WO2023044487A1 - Treatment of lung disease or injury using engineered antimicrobial peptides - Google Patents

Treatment of lung disease or injury using engineered antimicrobial peptides Download PDF

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Publication number
WO2023044487A1
WO2023044487A1 PCT/US2022/076667 US2022076667W WO2023044487A1 WO 2023044487 A1 WO2023044487 A1 WO 2023044487A1 US 2022076667 W US2022076667 W US 2022076667W WO 2023044487 A1 WO2023044487 A1 WO 2023044487A1
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Prior art keywords
arg
val
trp
seq
pharmaceutical composition
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PCT/US2022/076667
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French (fr)
Inventor
Jonathan D. STECKBECK
Bradd N. PICONE
John Michael SAUER
David Huang
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Peptilogics, Inc.
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Publication of WO2023044487A1 publication Critical patent/WO2023044487A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy

Definitions

  • Antibiotic resistance is a multifactorial problem, which can include (i) physiological changes, represented by the transition from the planktonic to the biofilm mode of growth and (ii) the acquisition of antibiotic resistance adaptive mutations facilitated by frequent mutator phenotypes. New treatments that are bactericidal against multidrug resistant strains, active against biofilm, and safe and tolerable are needed to treat recurrent acute and chronic lung infections in individuals with CF.
  • the present disclosure describes a method for treating or preventing a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg- Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-
  • the administering comprises an oral administration, an oronasal administration, an intra-nasal, an intra-tracheal, an inhalatory administration, an intravenous administration, or any combination thereof.
  • the present disclosure describes a method for treating or preventing a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17);
  • Described herein are methods comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject, wherein the subject has or is at risk of having an acute or chronic lung infection caused by cystic fibrosis (CF), wherein the pharmaceutical composition comprises a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp- Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-
  • the pharmaceutical composition comprises an aerosolized composition.
  • the lung disease or injury is pneumonia.
  • the lung disease or injury is acute or chronic lung infection.
  • the acute or chronic lung infection is caused by cystic fibrosis (CF).
  • the pharmaceutical composition comprises a dry powder formulation.
  • the administering further comprises using a nebulizer, a pressurized metered-dose inhaler (MDI) a mechanical ventilator a dry powder inhaler (DPI) a soft mist inhaler, or a concentrated aerosol generator.
  • MDI pressurized metered-dose inhaler
  • DPI dry powder inhaler
  • a concentrated aerosol generator a concentrated aerosol generator.
  • the nebulizer is a jet nebulizer, an ultrasonic nebulizer, or a vibrating mesh nebulizer. In some embodiments, the nebulizer is a vibrating mesh nebulizer.
  • the DPI is a single-dose DPI or multi-dose DPI. In some embodiments, the DPI is a reusable DPI or nonresuable DPI.
  • the pharmaceutical composition is a liquid composition. In some embodiments, the pharmaceutical composition is administered to a pulmonary system.
  • the pneumonia is hospital acquired pneumonia. In some embodiments, the hospital acquired pneumonia is ventilator acquired pneumonia.
  • the pneumonia is a bacterial pneumonia.
  • the bacterial pneumonia is caused by a bacteria selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, Staphylococcus lugdensis, methicillin-resistant Staphylococcus lugdensis, Staphylococcus haemolyticus, Staphylococcus spp., Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warngrass, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus pettenkoferi, Klebsiella pnuemoniae, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae, Enterobacter
  • the pneumonia is a viral pneumonia.
  • the viral pneumonia is caused by a virus selected from the group consisting of influenza, respiratory syncytial cytomegalovirus and any combination thereof
  • the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1).
  • the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 1. In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17).
  • the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 17.
  • the peptide or pharmaceutically acceptable salt thereof comprises any combination of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, SEQ ID NO 10, SEQ ID NO 11, SEQ ID NO 12, SEQ ID NO 13, SEQ ID NO 14, SEQ ID NO 15, SEQ ID NO 16, and SEQ ID NO 17.
  • the pharmaceutical composition comprises an osmolality value that is at least about 270 mOsm/kg to at least about 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 280 mOsm/kg.
  • the pharmaceutical composition comprises an osmolality value that is at least about 300 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 310 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is between about 280 mOsm/kg and 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises acetate. In some embodiments, the pharmaceutical composition comprises D-mannitol. In some embodiments, the pharmaceutical composition comprises D-trehalose. In some embodiments, the pharmaceutical composition comprises rh-HSA.
  • the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose.
  • the pharmaceutical composition is a dry powder.
  • the pharmaceutical composition is a liquid.
  • the pharmaceutical composition is an aerosol.
  • the pharmaceutical composition has a pH between 4.5 and 6.5. [0015] In some embodiments, the pH value is at least about 4.0 to at least about 5.5. In some embodiments the pH value is at least about 50 to at least about 55 In some embodiments the pH value is at least about 5.0. In some embodiments, the pH value is at least about 4.0 to at least about 5.5.
  • the pH value is at least about 5.5.
  • the method further comprises administering a neutrophil elastase.
  • the neutrophil elastase is human neutrophil elastase.
  • the method further comprises administering a lung surfactant.
  • the lung surfactant comprises about 25 mg/mL phospholipids, about 0.5-1.75 mg/mL triglycerides, about 1.4-3.5 mg/mL free fatty acids, and about 1.0 mg/mL protein.
  • the method further comprises inhibiting an inflammatory response.
  • the inflammatory response is quantified by measuring an expression level of tumor necrosis factor- ⁇ (TNF- ⁇ ) or interleukin-6 (IL-6).
  • TNF- ⁇ tumor necrosis factor- ⁇
  • IL-6 interleukin-6
  • the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.01 ⁇ g/mL to at least about 100 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.5 mg/mL to at least about 1 mg/mL.
  • the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 0.5 mg/mL to at least about 15 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 10 mg/mL. [0019] In some embodiments, the excipient is a salt.
  • the salt is selected from the group consisting of sodium, bicarbonate, sodium chloride, sodium lactate, potassium chloride, calcium chloride, magnesium chloride, and any combination thereof.
  • the pharmaceutical composition further comprises a pH buffering agent.
  • the pH buffering agent is selected from the group consisting of (4- (2-hydroxyethyl)-1-piperazineethanesulfonic acid), sodium hydrogen phosphate, sodium phosphate, magnesium phosphate, potassium dihydrogenphosphate, sodium bicarbonate, tris(hydroxymethyl)aminomethane, sodium citrate, and any combination thereof.
  • the pharmaceutical composition further comprises a pH adjusting agent.
  • the pH adjusting agent is hydrochloric acid, sodium hydroxide, ammonium hydroxide, or any combination thereof.
  • the excipient is a sugar.
  • the pharmaceutical composition further comprises a second antibiotic.
  • the second antibiotic is selected from the group consisting of piperacillin, tazobactam, cefepime, ceftazidime, ciprofloxacin, levofloxacin, amikacin, gentamicin, tobramycin, imipenem, meropenem, linesolid, vancomycin, and any combination thereof.
  • the pharmaceutical composition further comprises a propellant.
  • the propellant is 1,1,1,2-tetrafluoroethane or 1,1,-difluoroethane.
  • the pharmaceutical composition is administered to the subject at least once per day. In some embodiments, the pharmaceutical composition is administered to the subject at least twice per day. [0025] In some embodiments, the treating or preventing lasts over a course of at least about 1 day to at least about 10 years. In some embodiments, the course is at least about 12 months. In some embodiments, the course is at least about 2 months. In some embodiments, the course is at least about 1 months. In some embodiments, the course is at least about 2 weeks. [0026] In some embodiments, the pharmaceutical composition is in form of a unit dose.
  • the present disclosure describes a kit, comprising the pharmaceutical composition or the unit dose of any one of the proceeding claims and instructions for use of the pharmaceutical composition for treating or preventing pneumonia and a nebulizer.
  • the nebulizer is a vibrating mesh nebulizer.
  • an inhaler kit comprising the pharmaceutical compositions described herein in an inhaler and instructions for use of the pharmaceutical composition for treating or preventing lung disease or infection.
  • the pharmaceutical composition is a dry powder.
  • the pharmaceutical composition is a liquid.
  • the pharmaceutical composition is an aerosol.
  • the pharmaceutical composition has a pH between 4.5 and 6.5.
  • a pharmaceutical composition for administering by inhalation comprising: a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp- Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val- Val-Arg-Arg-Val-Arg-Arg-Val-Arg-Arg-Val-Arg-Arg-Val-Arg-Arg-Val-
  • the pharmaceutical composition is a dry powder. In some embodiments, the pharmaceutical composition is a liquid. In some embodiments, the pharmaceutical composition is an aerosol. In some embodiments, the osmolality value is between 270 mOsm/kg and 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises D-mannitol. In some embodiments, the pharmaceutical composition comprises D-trehalose. In some embodiments, the pharmaceutical composition comprises rh- HSA. In some embodiments, the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose. In some embodiments, the pharmaceutical composition further comprises a neutrophil elastase.
  • the neutrophil elastase is human neutrophil elastase.
  • FIG.1 schematically illustrates a protocol for minimum inhibitory concentration (MIC) assay of SEQ ID NO: 1 in the presence or in the absence of surfactant.
  • FIG.2 schematically illustrates study design for tolerability/PK (top panel) and efficacy (bottom panel). Animals will be rendered persistently neutropenic with cyclophosphamide administrations at Day -4, Day -1, Day +1 and Day +3 (circles).
  • Animals will not be infected in tolerability/PK study (top panel) but will be intranasally (IN) infected on Day 0 in the efficacy study (bottom panel).
  • the animals will be intratracheally (IT) and subcutaneously (SC) administered twice (BID, q12h) for 5 consecutive days. Dosing starts at 12 h post-infection for the 5 day dosing (bottom panel).
  • the tolerability/PK study follows the same study schedule as the efficacy study with sample collection at 0.25, 2, 12, 24, 48, 72, 96 and 120 h after the last dose (top panel).
  • FIG.3 schematically illustrates the mean TEER ( ⁇ *cm 2 ) from healthy human airway epithelial cells tissues exposed to test items or control treatments.
  • FIG.4 schematically illustrates the mean lactate dehydrogenase release from healthy human airway epithelial cells exposed to test item or control treatments.
  • FIG.5 schematically illustrates mean ATP content (%) from healthy human airway epithelial cells exposed to test item or control treatments.
  • FIG.6 shows mucociliary clearance from healthy human airway epithelial cells exposed to test item or control treatments.
  • FIG.7 shows the percent of active cilia from healthy human airway epithelial cells exposed to test item or control treatments.
  • FIG.8 shows the CBF results from healthy human airway epithelial cells exposed to test item or control treatments.
  • FIG.9 shows an image and heat map of healthy human airway epithelial cells during control CBF experiments (Air liquid interface).
  • FIG.10 shows an image and heat map of healthy human airway epithelial cells during CBF experiments (SEQ ID NO: 1 01 mg/mL)
  • FIG.11 shows an image and heat map of healthy human airway epithelial cells during CBF experiments (SEQ ID NO: 17, 1 mg/mL).
  • FIG.12 shows an image of polystyrene microbeads moving through the vehicle treated healthy human airway epithelial cells within the mucociliary clearance experiment.
  • FIG.13 shows an image of polystyrene microbeads moving though the high dose treated healthy human airway epithelial cells within the mucociliary clearance experiment.
  • FIG.14 schematically illustrates the mean TEER ( ⁇ *cm 2 ) from healthy human airway epithelial cells exposed to test items or control treatments.
  • FIG.15 schematically illustrates the mean total CFU results analyzed from healthy human airway epithelial cells exposed to test items or control treatments.
  • FIG.16 schematically illustrates the resulting CFU analyzed from healthy human airway epithelial cells exposed to test items or control treatments.
  • peptides that comprise antimicrobial, antiviral, antifungal or antitumor activity when administered to a subject.
  • a peptide described herein can be used to disrupt the integrity of a membrane by (a) binding to a negatively charged surface on a membrane; and/or (b) integrating into a membrane.
  • the ability of a peptide disclosed herein to bind to a negatively charged surface on a membrane and/or integrate into a membrane can allow a peptide to act as a toxic agent to cells with a negatively charged surface by disrupting membrane integrity.
  • a peptide disclosed herein can have anti-bacterial, anti-fungal, anti-mycotic, anti-parasitic, anti-protozoal, anti-viral, anti-infectious, anti-infective and/or germicidal, algicidal, amoebicidal, microbicidal, bactericidal, fungicidal, parasiticidal, protozoacidal, and/or protozoicidal properties.
  • the methods of treating a disease or condition described herein can be by administering to a subject a peptide or formulation containing a peptide as disclosed therein.
  • a peptide or formulation comprising a peptide described herein can be administered as an antimicrobial agent in order to at least partially inhibit the growth of a pathogen, such as bacteria, through disruption of the structural integrity of the bacterial cell membrane.
  • a peptide described herein can be screened for broad spectrum activity against a variety of pathogens for broad utility when administered to a subject.
  • An antimicrobial peptide described herein can also be used as a means to produce an antimicrobial film for coating a device.
  • the peptides disclosed herein can be used to coat the interior and/or exterior of a medical device, for example, an implantable medical device.
  • the coating of a device with a peptide disclosed herein can reduce the growth and proliferation of cells, bacteria, fungi or virus on a surface coated with a peptide.
  • coating an implantable medical device with a peptide disclosed herein can reduce the risk of an infection to a subject upon implanting the medical device in a subject.
  • a peptide described herein or formulation comprising a peptide described herein can be included in a kit.
  • the kit can be utilized, for example, by a subject or healthcare professional to coat a device or to treat a condition or disease described herein.
  • the antimicrobial peptides may be derived from, and are analogs of, the LLP-1 peptide parent sequence corresponding to amino acids 828- 856 of the HIV-l viral isolate HXB2R Env, (see Table 1 below).
  • the antimicrobial activity of other LLP-1 peptide analogues has been previously described (see, Tencza et al., 1999, Journal of Antimicrobial Chemotherapy 44:33-41, U.S. Patent No.5,714,577 of Montelaro et al. and U.S. Patent No.5,945,507 of Montelaro et al., the disclosures of which are incorporated herein by reference).
  • the antimicrobial peptides may be LLP-1 analogs having modifications based on the following principles: (i) optimizing amphipathicity, (ii) substituting arginine (Arg) on the charged face and/or valine (Val) or tryptophan (Trp) on the hydrophobic face with another amino acid, and (iii) increasing peptide length; see Table 1). Amino acid sequences are provided, left-to-right, from their N-terminus to their C-terminus in 1 letter designations and 3 letter designations. Table 1.
  • the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 1.
  • the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 2. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 3. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 4. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 5. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 6. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 7. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 8.
  • the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 9. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 10. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 11. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 12. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 13. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 14. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 15.
  • the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 16. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 17. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 18. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 19. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 20. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 21. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 22.
  • the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 23 In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 24. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 25.
  • the peptide or pharmaceutically acceptable salt thereof has at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 1, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 2, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 3, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 4, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 5, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 6, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 7, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 8, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 9, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 10, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 11, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 12, at least 70% sequence identify to
  • the peptide or pharmaceutically acceptable salt thereof has at least 75%, 80%, 85%, 90%, 95%, or 99% sequence identify to a polypeptide sequence listed in Table 1 and any increments of percentage therebetween.
  • the pharmaceutical formulation comprises at least one peptide described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises one or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises two or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises three or more peptides described herein as listed in Table 1.
  • the pharmaceutical formulation comprises four or more peptides described herein as listed in Table 1 In some embodiments the pharmaceutical formulation comprises five or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises six or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises seven or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises eight or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises nine or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises ten or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises eleven or more peptides described herein as listed in Table 1.
  • the pharmaceutical formulation comprises twelve or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises thirteen or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises fourteen or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises fifteen or more peptides described herein as listed in Table 1. [0057]
  • a peptide disclosed herein can be a salt thereof. In some embodiments, recitation of the phrases “peptide” or “polypeptide” should be construed to include a salt thereof even if not explicitly recited.
  • a salt can include a carboxylate salt (e.g.
  • a sulfonate salt e.g. benzene sulfonate, methyl-, bromo- or chloro- benzenesulfonate, xylenesulfonate, methanesulfonate, trifluoromethanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2- naphthalene-sulfonate or 1,5- naphthalenedisulfonate salts); a sulfate salt; a pyrosulfate salt; a bisulfate salt; a sulfite salt; a bisulfite salt; a phosphate salt; a monohydrogenphosphate salt; a dihydrogenphosphate salt; a metaphosphate salt; a pyrophosphate salt; a nitrate salt; a chromium salt (e.g. benzene sulfonate,
  • amino acids of the peptides described herein can be L-amino acids. In some embodiments, amino acids of the peptides described herein can be D-amino acids. In some embodiments the peptides can have 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 D-amino acids and the rest are L-amino acids within the peptide sequence.
  • the peptides can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 L-amino acids and the rest are D- amino acids within the peptide sequence.
  • a peptide can be formulated with one or more pharmaceutically acceptable salts.
  • a pharmaceutically acceptable salt can be a salt described in Berge et al, J. Pharm. Sci, 1977.
  • a pharmaceutically acceptable salts can include those salts prepared by reaction of a peptide with a mineral, organic acid or inorganic base, such salts including, acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bitartrate, bromide, butyrate, butyn-1,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne-1,6-
  • metaphosphate methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1- napthalenesulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3- phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, undeconate and xylenesulfonate.
  • a peptide can be formulated as a cleavable prodrug.
  • prodrug can refer to a drug precursor that, following administration to a subject and subsequent absorption, can be converted to an active, or a more active species via some process, such as conversion by a metabolic pathway.
  • the term can encompass a derivative, which, upon administration to a recipient, can be capable of providing, either directly or indirectly, a peptide, pharmaceutically acceptable salt or a metabolite or residue thereof.
  • Some prodrugs can have a chemical group present on a prodrug that renders it less active and/or confers solubility or some other property to the drug.
  • a prodrugs can be a prodrug that can increase the bioavailability of a peptide when administered to a subject (e.g., by allowing an administered peptide to be more readily absorbed) or which enhance delivery of the peptide to a biological compartment (eg the brain or lymphatic system)
  • a biological compartment e.g the brain or lymphatic system
  • the pharmaceutical composition described herein may comprises a pH value of about 4.5 to about 6.5.
  • the pharmaceutical composition may comprise a pH value from 4.5 to 6.5, including increments therebetween, such as 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, or 6.5, including increments therebetween.
  • the pharmaceutical formulation described herein may further comprise a pH value of about 3.5 to about 5.5.
  • the pharmaceutical composition may comprise a pH value from 3.5 to 5.5, including increments therebetween, such as 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, or 5.5, including increments therebetween.
  • the pharmaceutical composition has a pH of about 3.5.
  • the pharmaceutical composition has a pH of about 3.6.
  • the pharmaceutical composition has a pH of about 3.7.
  • the pharmaceutical composition has a pH of about 3.8.
  • the pharmaceutical composition has a pH of about 3.9.
  • the pharmaceutical composition has a pH of about 4.0. In some embodiments, the pharmaceutical composition has a pH of about 4.1. In some embodiments, the pharmaceutical composition has a pH of about 4.2. In some embodiments, the pharmaceutical composition has a pH of about 4.3. In some embodiments, the pharmaceutical composition has a pH of about 4.4. In some embodiments, the pharmaceutical composition has a pH of about 4.5. In some embodiments, the pharmaceutical composition has a pH of about 4.6. In some embodiments, the pharmaceutical composition has a pH of about 4.7. In some embodiments, the pharmaceutical composition has a pH of about 4.8. In some embodiments, the pharmaceutical composition has a pH of about 4.9. In some embodiments, the pharmaceutical composition has a pH of about 5.0.
  • the pharmaceutical composition has a pH of about 5.1. In some embodiments, the pharmaceutical composition has a pH of about 5.2. In some embodiments, the pharmaceutical composition has a pH of about 5.3. In some embodiments, the pharmaceutical composition has a pH of about 5.4. In some embodiments, the pharmaceutical composition has a pH of about 5.5. In some embodiments, the pharmaceutical composition may have a pH value of about a physiological value (about 7.1 to about 7.5). In some embodiments, the pharmaceutical composition may have a basic pH value of about 8.0 to 9.0.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.6 to at least 5.5, at least 3.7 to at least 5.5, at least 3.8 to at least 5.5, at least 3.9 to at least 5.5, at least 4.0 to at least 5.5, at least 4.1 to at least 5.5, at least 4.2 to at least 5.5, at least 4.3 to at least 5.5, at least 44 to at least 55 at least 45 to at least 55 at least 46 to at least 55 at least 47 to at least 5.5, at least 4.8 to at least 5.5, at least 4.9 to at least 5.5, at least 5.0 to at least 5.5, at least 5.1 to at least 5.5, at least 5.2 to at least 5.5, at least 5.3 to at least 5.5, or at least 5.4 to at least 5.5.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.5 to at least 5.4, at least 3.5 to at least 5.3, at least 3.5 to at least 5.2, at least 3.5 to at least 5.1, at least 3.5 to at least 5.0, at least 3.5 to at least 4.9, at least 3.5 to at least 4.8, at least 3.5 to at least 4.7, at least 3.5 to at least 4.6, at least 3.5 to at least 4.5, at least 3.5 to at least 4.4, at least 3.5 to at least 4.3, at least 3.5 to at least 4.2, at least 3.5 to at least 4.1, at least 3.5 to at least 4.0, at least 3.5 to at least 3.9, at least 3.5 to at least 3.8, at least 3.5 to at least 3.7, or at least 3.5 to at least 3.6.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.6 to at least 5.4, at least 3.7 to at least 5.3, at least 3.8 to at least 5.2, at least 3.9 to at least 5.1, at least 4.0 to at least 5.0, at least 4.1 to at least 4.9, at least 4.2 to at least 4.8, at least 4.3 to at least 4.7, at least 4.4 to at least 4.6, at least 4.0 to about 5.5, at least 4.5 to about 5.5, at least 5.0.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.6 to at most 5.5, at most 3.7 to at most 5.5, at most 3.8 to at most 5.5, at most 3.9 to at most 5.5, at most 4.0 to at most 5.5, at most 4.1 to at most 5.5, at most 4.2 to at most 5.5, at most 4.3 to at most 5.5, at most 4.4 to at most 5.5, at most 4.5 to at most 5.5, at most 4.6 to at most 5.5, at most 4.7 to at most 5.5, at most 4.8 to at most 5.5, at most 4.9 to at most 5.5, at most 5.0 to at most 5.5, at most 5.1 to at most 5.5, at most 5.2 to at most 5.5, at most 5.3 to at most 5.5, or at most 5.4 to at most 5.5.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.5 to at most 5.4, at most 3.5 to at most 5.3, at most 3.5 to at most 5.2, at most 3.5 to at most 5.1, at most 3.5 to at most 5.0, at most 3.5 to at most 4.9, at most 3.5 to at most 4.8, at most 3.5 to at most 4.7, at most 3.5 to at most 4.6, at most 3.5 to at most 4.5, at most 3.5 to at most 4.4, at most 3.5 to at most 4.3, at most 3.5 to at most 4.2, at most 3.5 to at most 4.1, at most 3.5 to at most 4.0, at most 3.5 to at most 3.9, at most 3.5 to at most 3.8, at most 3.5 to at most 3.7, or at most 3.5 to at most 3.6.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.6 to at most 5.4, at most 3.7 to at most 5.3, at most 3.8 to at most 5.2, at most 3.9 to at most 5.1, at most 4.0 to at most 5.0, at most 4.1 to at most 4.9, at most 4.2 to at most 4.8, at most 4.3 to at most 4.7, at most 4.4 to at most 4.6, at most 4.0 to about 5.5, at most 4.5 to about 5.5, at most 5.0.
  • the pharmaceutical composition may further comprise a pH adjusting agent such as hydrochloric acid sodium hydroxide ammonium hydroxide other pH adjusting agents known to those skilled in the art, or combinations thereof to the aqueous carrier.
  • a pH adjusting agent such as hydrochloric acid sodium hydroxide ammonium hydroxide other pH adjusting agents known to those skilled in the art, or combinations thereof to the aqueous carrier.
  • the pH adjusting agent is hydrochloric acid.
  • the pH adjusting agent is sodium hydroxide.
  • the pH adjusting agent is ammonium hydroxide.
  • the pH adjusting agent is hydrochloric acid, sodium hydroxide, or any combination thereof.
  • the pharmaceutical composition further comprises a pH buffer or pH buffering agent.
  • Non-limiting examples of suitable pH buffers or pH buffering agents includes sodium citrate, citric acid, sodium acetate, acetic acid, phosphoric acid, trisodium phosphate, lactic acid, sodium lactate, tartaric acid, monosodium tartrate, sodium tartrate dibasic, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), piperazine-N,N′-bis(2- ethanesulfonic acid) (PIPES), 2-(N-morpholino)ethanesulfonic acid (MES), other pH buffers known to those skilled in the art, or combinations thereof.
  • the pH buffer or pH buffering agent comprises sodium citrate.
  • the pH buffer or pH buffering agent comprises citric acid. some embodiments, the pH buffer or pH buffering agent comprises sodium acetate. In some embodiments, the pH buffer or pH buffering agent comprises acetic acid. In some embodiments, the pH buffer or pH buffering agent comprises phosphoric acid. In some embodiments, the pH buffer or pH buffering agent comprises trisodium phosphate. In some embodiments, the pH buffer or pH buffering agent comprises lactic acid. In some embodiments, the pH buffer or pH buffering agent comprises sodium lactate. In some embodiments, the pH buffer or pH buffering agent comprises tartaric acid. In some embodiments, the pH buffer or pH buffering agent comprises monosodium tartrate.
  • the pH buffer or pH buffering agent comprises sodium tartrate dibasic. In some embodiments, the pH buffer or pH buffering agent comprises 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES). In some embodiments, the pH buffer or pH buffering agent comprises piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES). In some embodiments, the pH buffer or pH buffering agent comprises 2-(N-morpholino)ethanesulfonic acid (MES).
  • HPES 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid
  • PPES piperazine-N,N′-bis(2-ethanesulfonic acid)
  • the pH buffer or pH buffering agent comprises 2-(N-morpholino)ethanesulfonic acid (MES).
  • the pH buffer or pH buffering agent comprises sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, potassium hydrogen phosphate, glycine, tris(hydroxymethyl)aminomethane, and any combination thereof.
  • the pH buffer or pH buffering agent comprises sodium hydrogen phosphate.
  • the pH buffer or pH buffering agent comprises sodium dihydrogen phosphate.
  • the pH buffer or pH buffering agent comprises potassium dihydrogen phosphate.
  • the pH buffer or pH buffering agent comprises potassium hydrogen phosphate.
  • the pH buffer or pH buffering agent comprises glycine
  • the pH buffer or pH buffering agent comprises tris(hydroxymethyl)aminomethane.
  • the pH buffer comprises a phosphate buffer.
  • the phosphate buffer comprises Dulbecco’s phosphate buffered saline (dPBS).
  • the pH buffering agent comprises at least one of: (4-(2- hydroxyethyl)-1-piperazineethanesulfonic acid), sodium hydrogen phosphate, sodium phosphate, magnesium phosphate, potassium dihydrogenphosphate, sodium bicarbonate, tris(hydroxymethyl)aminomethane, sodium citrate, or any combination thereof.
  • the pharmaceutical formulation can be free of a pH buffering agent or pH buffer.
  • At least one peptide disclosed herein can be formulated as a pharmaceutical formulation.
  • a pharmaceutical formulation can comprise a peptide described herein and at least one excipient.
  • pharmaceutically acceptable it is meant that the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
  • compatible means that the components of the formulation are capable of being commingled with the subject compound, and with each other, in a manner such that there is no interaction that would substantially reduce the pharmaceutical efficacy of the formulation under ordinary use situations.
  • a pharmaceutical formulation can comprise an excipient.
  • An excipient can be an excipient described in the Handbook of Pharmaceutical Excipients, American Pharmaceutical Association (1986).
  • the excipient comprises acetate.
  • the excipient comprises D-mannitol.
  • the excipient comprises D-trehalose.
  • the excipient comprises human serum albumin.
  • the excipient comprises sorbitol.
  • the excipient comprises saccharin.
  • the excipient comprises sucrose.
  • the excipient comprises povidone.
  • the excipient comprises crospovidone.
  • the excipient comprises hydroxypropylcellulose.
  • suitable excipients can include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a chelator, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and/or a coloring agent.
  • the pharmaceutical formulation further comprises one or more additional pharmaceutically acceptable excipients. See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21 st Ed. Mack Pub. Co., Easton, PA (2005) for a list of pharmaceutically acceptable excipients.
  • the pharmaceutically acceptable excipient is of sufficiently high purity and sufficiently low toxicity to render them suitable for administration preferably to an animal preferably a mammal being treated
  • an excipient can comprise a preservative.
  • suitable preservatives can include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.
  • Antioxidants can further include but not limited to EDTA, citric acid, ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), sodium sulfite, p-amino benzoic acid, glutathione, propyl gallate, cysteine, methionine, ethanol and N- acetyl cysteine.
  • BHT butylated hydroxytoluene
  • BHA butylated hydroxy anisole
  • sodium sulfite sodium sulfite
  • glutathione propyl gallate
  • cysteine methionine
  • ethanol N- acetyl cysteine
  • a preservatives can include validamycin A, TL-3, sodium ortho vanadate, sodium fluoride, N-a-tosyl-Phe- chloromethylketone, N-a-tosyl-Lys-chloromethylketone, aprotinin, phenylmethylsulfonyl fluoride, diisopropylfluorophosphate, kinase inhibitor, phosphatase inhibitor, caspase inhibitor, granzyme inhibitor, cell adhesion inhibitor, cell division inhibitor, cell cycle inhibitor, lipid signaling inhibitor, protease inhibitor, reducing agent, alkylating agent, antimicrobial agent, oxidase inhibitor, or other inhibitor.
  • an excipient can comprise a binder.
  • suitable binders can include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C 12 -C 18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.
  • the binders that can be used in a pharmaceutical formulation can be selected from starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol and water or a combination thereof.
  • an excipient can comprise a lubricant.
  • suitable lubricants can include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.
  • the lubricants that can be used in a pharmaceutical formulation can be selected from metallic stearates (such as magnesium stearate, calcium stearate, aluminium stearate), fatty acid esters (such as sodium stearyl fumarate), fatty acids (such as stearic acid), fatty alcohols, glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oils, leucine, polyethylene glycols (PEG), metallic lauryl sulphates (such as sodium lauryl sulphate, magnesium lauryl sulphate), sodium chloride, sodium benzoate, sodium acetate and talc or a combination thereof.
  • an excipient can comprise a dispersion enhancer.
  • Non-limiting examples of suitable dispersants can include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
  • an excipient can comprise a disintegrant.
  • a disintegrant can be a non-effervescent disintegrant.
  • Non-limiting examples of suitable non- effervescent disintegrants can include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth.
  • a disintegrant can be an effervescent disintegrant.
  • suitable effervescent disintegrants can include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.
  • an excipient can comprise a flavoring agent.
  • Flavoring agents incorporated into an outer layer can be chosen from synthetic flavor oils and flavoring aromatics; natural oils; extracts from plants, leaves, flowers, and fruits; and combinations thereof.
  • a flavoring agent can be selected from the group consisting of cinnamon oils; oil of wintergreen; peppermint oils; clover oil; hay oil; anise oil; eucalyptus; vanilla; citrus oil such as lemon oil, orange oil, grape and grapefruit oil; and fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple, and apricot.
  • an excipient can comprise a sweetener.
  • Non-limiting examples of suitable sweeteners can include glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as a sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; and sugar alcohols such as sorbitol, mannitol, sylitol, and the like.
  • the excipient may be a sugar.
  • Non-limiting examples of suitable sugars can include glucose, sucrose, dextrose, lactose, maltodextrin, fructose, and mixtures thereof.
  • an excipient can comprise a coloring agent.
  • suitable color agents can include food, drug and cosmetic colors (FD&C), drug and cosmetic colors (D&C), and external drug and cosmetic colors (Ext. D&C).
  • a coloring agent can be used as dyes.
  • an excipient can comprise an isotonicity agent.
  • an excipient can comprise a chelator.
  • a chelator can be a fungicidal chelator.
  • Examples can include, but are not limited to: ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA); a disodium, trisodium, tetrasodium, dipotassium, tripotassium, dilithium and diammonium salt of EDTA; a barium, calcium, cobalt, copper, dysprosium, europium, iron, indium, lanthanum, magnesium, manganese, nickel, samarium, strontium, or zinc chelate of EDTA; trans-1,2-diaminocyclohexane-N,N,N',N'- tetraaceticacid monohydrate; N,N-bis(2-hydroxyethyl)glycine; 1,3-diamino-2-hydroxypropane- N,N,N',N'-tetraacetic acid; 1,3-diaminopropane-N,N,N',N'-tetraacetic acid;
  • an excipient can comprise a diluent.
  • diluents can include water, glycerol, methanol, ethanol, and other similar biocompatible diluents.
  • a diluent can be an aqueous acid such as acetic acid, citric acid, maleic acid, hydrochloric acid, phosphoric acid, nitric acid, sulfuric acid, or similar.
  • a diluent can be selected from a group comprising alkaline metal carbonates such as calcium carbonate; alkaline metal phosphates such as calcium phosphate; alkaline metal sulphates such as calcium sulphate; cellulose derivatives such as cellulose, microcrystalline cellulose, cellulose acetate; magnesium oxide, dextrin, fructose, dextrose, glyceryl palmitostearate, lactitol, caoline, lactose, maltose, D-mannitol, simethicone, sorbitol, starch, pregelatinized starch, talc, xylitol and/or anhydrates, hydrates and/or pharmaceutically acceptable derivatives thereof or combinations thereof.
  • alkaline metal carbonates such as calcium carbonate
  • alkaline metal phosphates such as calcium phosphate
  • alkaline metal sulphates such as calcium sulphate
  • cellulose derivatives such as cellulose, microcrystalline cellulose, cellulose
  • an excipient can comprise a surfactant.
  • Surfactants can be selected from, but not limited to, polyoxyethylene sorbitan fatty acid esters (polysorbates), sodium lauryl sulphate, sodium stearyl fumarate, polyoxyethylene alkyl ethers, sorbitan fatty acid esters, polyethylene glycols (PEG), polyoxyethylene castor oil derivatives, docusate sodium, quaternary ammonium compounds, amino acids such as L- leucine, sugar esters of fatty acids, glycerides of fatty acids or a combination thereof [0082]
  • an excipient can comprise an aqueous carrier.
  • the aqueous carrier is lactated Ringer’s solution, normal saline (0.9% w/v), or aqueous sodium carbonate. In some embodiments, the aqueous carrier is lactated Ringer’s solution. In some embodiments, the aqueous carrier is normal saline (0.9% w/v). In some embodiments, the aqueous carrier is aqueous sodium bicarbonate. In some embodiments, the aqueous carrier is physiologically isotonic, physiologically hypotonic, or physiologically hypertonic. In some embodiments, the aqueous carrier is physiologically isotonic. In some embodiments, the aqueous carrier is physiologically hypotonic.
  • the aqueous carrier is physiologically hypotonic (sub-physiologic osmolarity or osmolality), for example, modified versions of lactated Ringer’s solution, normal saline (0.9% w/v), or aqueous sodium bicarbonate diluted with water.
  • the aqueous carrier is physiologically hypertonic.
  • the aqueous carrier has a total osmolarity ranging from about 1 milliosmole per one liter (mOsm/L) to about 5,000 mOsm/L.
  • the aqueous carrier has a total osmolarity of about 1 mOsm/L, about 50 mOsm/L, about 100 mOsm/L, about 150 mOsm/L, about 200 mOsm/L, about 250 mOsm/L, about 300 mOsm/L, about 350 mOsm/L, about 400 mOsm/L, about 450 mOsm/L, about 500 mOsm/L, about 1000 mOsm/L, about 1500 mOsm/L, about 2000 mOsm/L, about 2500 mOsm/L, about 3000 mOsm/L, about 3500 mOsm/L, about 4000 mOsm/L, about 4500 mOsm/L, or about 5000 mOsm/L.
  • the aqueous carrier has a total osmolality ranging from about 1 milliosmole per kilogram (mOsm/kg) from 5000 mOsm/kg. In some embodiments, the aqueous carrier has a total osmolarity of about 1 mOsm/kg, about 50 mOsm/kg, about 100 mOsm/kg, about 150 mOsm/kg, about 200 mOsm/kg, about 250 mOsm/kg, about 300 mOsm/kg, about 350 mOsm/kg, about 400 mOsm/kg, about 450 mOsm/kg, about 500 mOsm/kg, about 1000 mOsm/kg, about 1500 mOsm/kg, about 2000 mOsm/kg, about 2500 mOsm/kg, about 3000 mOsm/kg, about 3500 mOsm/kg, about 4000 mOsm
  • the pharmaceutical composition comprises an osmolality value of about 270 mOsm/kg to about 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 270 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 280 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 290 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 300 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 310 mOsm/kg.
  • the pharmaceutical composition comprises an osmolality value of at least about 320 mOsm/kg In some embodiments the pharmaceutical composition comprises an osmolality value of at least about 330 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 340 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 350 mOsm/kg. In some embodiments, the aqueous carrier may have a total ionic strength ranging from about 0.001 molar (M) and 1.0 M.
  • aqueous carrier may have a total ionic strength of about 0.001 M, about 0.01 M, about 0.015 M, about 0.02 M, about 0.025 M, about 0.03 M, about 0.035 M, about 0.04 M, about 0.05 M, about 0.055 M, about 0.06 M, about 0.065 M, about 0.07 M, about 0.075 M, about 0.08 M, about 0.085 M, about 0.09 M, about 0.1 M, about 0.12 M, about 0.14 M, about 0.15 M, about 0.16 M, about 0.18 M, about 0.2 M, about 0.22 M, about 0.24 M, about 0.25 M, about 0.26 M, about 0.28 M, about 0.03 M, about 0.35 M, about 0.4 M, about 0.45 M, about 0.5 M, about 0.55 M, about 0.6 M, about 0.65 M, about 0.7 M, about 0.75 M about 0.8 M, about 0.85 M, about 0.9 M, about 0.95 M, or about 1.0 M.
  • the pharmaceutical formulation is in the form of a tablet, a liquid, a syrup, an oral formulation, an intravenous formulation, an intranasal formulation, an ocular formulation, an otic formulation, a subcutaneous formulation, an inhalation formulation, a suppository, and any combination thereof.
  • a weight fraction of an excipient or combination of excipients in a pharmaceutical formulation can be less than about 80%, 70%, 60%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, or 1% as compared to a total weight of a pharmaceutical formulation. See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21 st Ed.
  • the lung disease or injury is pneumonia.
  • the pneumonia is a viral pneumonia.
  • the viral pneumonia is caused by a virus selected from influenza, respiratory syncytial, cytomegalovirus, and any combination thereof.
  • the the pneumonia is a bacterial pneumonia.
  • the bacterial pneumonia is caused by a bacteria selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, Staphylococcus lugdensis, methicillin-resistant Staphylococcus lugdensis, Staphylococcus haemolyticus, Staphylococcus spp., Staphylococcus hominis, Staphylococcus saprophyticus Staphylococcus simulans Staphylococcus warnerii Staphylococcus capitis Staphylococcus caprae, Staphylococcus pettenkoferi, Klebsiella pnuemoniae, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae, Enterobacter species, Cintrobacter species, Stenotrophomonas malt
  • the bacteria can be antibiotic-tolerant or antibiotics-resistant.
  • the pneumonia can arise from the subject being exposed to bacteria in a hospital setting.
  • the pneumonia can arise from a ventilator.
  • biofilms may be formed on a living (e.g., lung) or non-living surface (e.g., catheters, endotracheal tubes, etc.).
  • the pneumonia is hospital acquired pneumonia.
  • the pneumonia is ventilator acquired pneumonia.
  • the lung disease or injury is an acute lung infection or a chronic lung infection. In some embodiments, the lung disease or injury is caused by cystic fibrosis.
  • administering the pharmaceutical composition described herein may comprise an oral administration, an oronasal administration, an intra-nasal, an intra-trachael, an inhalatory administration, an intravenous administration, any other administrative routes known to those skilled in the art, or any combination thereof.
  • administration of the peptide or pharmaceutically acceptable salt may be administered in formulations containing conventionally acceptable carriers, adjuvants, and vehicles as desired.
  • administration of the pharmaceutical composition further comprises administration of neutrophil elastase.
  • the neutrophil elastase is human neutrophil elastase.
  • the administration may be through injection or infusion, including intra-arterial, intracardiac, intraperitoneal, intrathecal, intravascular, intravenous, subcutaneous, inhalational, transdermal, transmucosal, sublingual, buccal, dermal, intranasal, any other method of administration known to those skilled in the art, or any combinations thereof.
  • the method may comprise draining liquid in the lungs (thoracentesis) prior to administering the pharmaceutical composition described herein.
  • the method can further comprise administering an additional antibiotic or an antiviral compound.
  • an antibiotic course can be administered before, during, or after administering the pharmaceutical composition described herein.
  • the method of administration may last over a course of at least about 1 hour, 5 hours, 12 hours, 24 hours, 48 hours, 72 hours, 4 days, 5 days, 1 week, 2 weeks, 3 week, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 20 years, 25 years, 30 years, 35 years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years, 70 years, 75 years, or 80 years.
  • Administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt thereof may be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times a day.
  • pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be delivered more than once a day.
  • peptide or pharmaceutically acceptable salt present may be delivered more than twice a day.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 1 day to at least about 12 months.
  • the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 2 months.
  • pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 1 months. In some embodiments, pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 2 weeks. [0093] In some embodiments, administration of a pharmaceutical composition comprising a peptide may be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 times a week.
  • administration of a peptide, salt, or pharmaceutical composition comprising a peptide may be performed at least 1 2 3 4 5 6 7 8 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90 times a month.
  • the method disclosed herein can lead to at least about 10% reduction in bacterial burden, at least about 20% reduction in bacterial burden, at least about 30% reduction in bacterial burden, at least about 40% reduction in bacterial burden, at least about 50% reduction in bacterial burden, at least about 60% reduction in bacterial burden, at least about 70% reduction in bacterial burden, at least about 80% reduction in bacterial burden, at least about 90% reduction in bacterial burden, at least about 90% reduction in bacterial burden, at least about 91% reduction in bacterial burden, at least about 92% reduction in bacterial burden, at least about 93% reduction in bacterial burden, at least about 94% reduction in bacterial burden, at least about 95% reduction in bacterial burden, at least about 96% reduction in bacterial burden, at least about 97% reduction in bacterial burden, at least about 98% reduction in bacterial burden, at least about 99% reduction in bacterial burden, at least about 99.9% reduction in bacterial burden, at least about 99.99% reduction in bacterial burden, or any increments therebetween.
  • administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may occur over a time period of from at least about 0.5 min to at least about 30 min. In some embodiments, delivery of pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may occur over a time period of at least about 15 min.
  • administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt occurs over a time period of from at least about 0.5 min to at least about 1 min, from at least about 1 min to at least about 2 min, from at least about 2 min to at least about 3 min, from at least about 3 min to at least about 4 min, from at least about 4 min to at least about 5 min, from at least about 5 min to at least about 6 min, from at least about 6 min to at least about 7 min, from at least about 7 min to at least about 8 min, from at least about 8 min to at least about 9 min, from at least about 9 min to at least about 10 min, from at least about 10 min to at least about 11 min, from at least about 11 min to at least about 12 min, from at least about 12 min to at least about 13 min, from at least about 13 min to at least about 14 min, from at least about 14 min to at least about 15 min, from at least about 15 min to at least about 16 min, from at least about 16 min to at least about 17 min,
  • the pharmaceutical formulation described herein may have an anti-inflammatory effect on a subject.
  • the anti-inflammatory effect may be inhibiting a cytokine response in the subject during the treatment for pneumonia or other chronic lung disease, such as cystic fibrosis.
  • the anti-inflammatory effect may be reducing the levels of a cytokine due to an infection.
  • the anti- inflammatory effect may be reducing the rise in the levels of a cytokine due to said infection.
  • the cytokine may comprise at least one of: interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin- 9, interleukin-10, interleukin-11, interleukin-12, interleukin-13, interleukin-14, interleukin-15, interleukin-16, interleukin-17, interleukin-18, interleukin-19, interleukin-20, interleukin-21, interleukin-22, interleukin-23, interleukin-24, interleukin-25, interleukin-26, interleukin-27, interleukin-28, interleukin-29, interleukin-30, interleukin-31, interleukin-32, interleukin-33, interleukin-34, interleukin-35, interleukin-36, a chemokine, an interferon
  • the anti-inflammatory effect may be reducing tissue destruction caused by inflammation. In some embodiments, the anti-inflammatory effect may be reducing tissue destruction caused by an infection. INHALATION FORMULATION AND ADMINISTRATION [0099]
  • the described pharmaceutical composition here is in the form of an inhalation formulation. In some embodiments, the described pharmaceutical composition comprises a dry powder formulation. In other embodiments, the described pharmaceutical composition comprises a liquid formulation. In some embodiments, inhalation of the pharmaceutical composition described herein may be facilitated by an aerosolization device or inhaler.
  • the aerosolization device or inhaler is a nebulizer, a pressurized metered-dose inhaler (MDI), a mechanical ventilator, a soft mist inhaler, a concentrated aerosol generator, or a dry powder inhaler (DPI).
  • MDI pressurized metered-dose inhaler
  • DPI dry powder inhaler
  • Efficient drug delivery to the lungs through nebulizers is dependent on several factors including inhaler device, formulation, and inhalation maneuver.
  • the aerosolization device or inhaler is dependent on the pharmaceutical composition in the form of a liquid.
  • the aerosolization device or inhaler is dependent on the pharmaceutical composition in the form of a solid or an inhalable dry powder.
  • a nebulizer is selected on the basis of allowing the formation of an aerosol of the pharmaceutical composition described herein.
  • Nebulizers can impart energy into a liquid pharmaceutical composition to aerosolize the liquid, and to allow delivery to the pulmonary system, e.g., the lungs, of a patient.
  • a nebulizer comprises a liquid delivery system, such as a container having a reservoir that contains a liquid pharmaceutical composition.
  • the aerosolization device can comprise the extrusion of the pharmaceutical preparation through micron or submicron-sized holes with subsequent Rayleigh break-up into fine droplets.
  • an inhaler can comprise a canister containing the droplets or droplets and propellant, and wherein the inhaler comprises a metering valve in communication with an interior of the canister.
  • the propellant can be a hydrofluoroalkane.
  • the pharmaceutical composition can be in liquid solution, and can be administered with nebulizers, in order to provide an aerosolized medicament that can be administered to the pulmonary air passages of a patient in need thereof. Nebulizers known in the art can easily be employed for administration of the claimed formulations.
  • the propellant is a fluorocarbon.
  • the fluorocarbon is a perfluorocarbon.
  • the fluorocarbon is a partially fluorinated carbon.
  • the propellant is a pharmaceutically acceptable fluorocarbon.
  • the propellant is 1,1,1,2-tetrafluoroethane (HFA 134a).
  • the propellant is 1,1-difluoroethane (HFA 152a).
  • the nebulizer is an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.
  • the nebulizer is jet nebulizer, an ultrasonic nebulizer, or a vibrating mesh nebulizer.
  • the nebulizer is a breath activated or breath-actuated nebulizer.
  • the nebulizer is a hand-held inhaler device (e.g., a Breath Actuated Nebulizer (BAN)).
  • the nebulizer has a compressed air source.
  • the nebulizer converts the liquid pharmaceutical composition into an aerosol.
  • the nebulizer converts liquid medication into an aerosol by extruding the pharmaceutical preparation through micron or submicron-sized holes.
  • the nebulizer converts liquid medication into an aerosol so it can be inhaled into the lungs.
  • the nebulizer is a small volume nebulizer.
  • aerosolized medication is only produced when inhaled through the device.
  • a jet nebulizer that utilizes compressed gas is forced through an orifice in the container may be used to administer the liquid pharmaceutical composition.
  • the compressed gas forces liquid to be withdrawn through a nozzle, and the withdrawn liquid can mix with the flowing gas to form aerosol droplets.
  • a cloud of droplets can then be administered to the patient’s respiratory tract.
  • the nebulizer is a small volume jet nebulizer.
  • the nebulizer is a vibrating mesh nebulizer. In some embodiments, the vibrating mesh nebulizer uses mechanical energy to vibrates a mesh.
  • nebulizers include, but are not limited to, the Aeroneb®Go or Aeroneb®Pro nebulizers, available from Aerogen Ltd. of Galway, Ireland; the PARI eFlow and other PARI nebulizers available from PARI Respiratory Equipment, Inc. of Midlothian, Va.; the Lumiscope® Nebulizer 6600 or 6610 available from Lumiscope Company, Inc. of East Brunswick, N.J.; and the Omron NE-U22 available from Omron Healthcare, Inc. of Kyoto, Japan.
  • nebulizers include devices produced by Medspray (Enschede, The Netherlands).
  • the vibrating mesh nebulizer can be used without compressed gas.
  • the aerosolized pharmaceutical composition can be introduced without substantially affecting the flow characteristics.
  • the generated droplets when using a nebulizer of this type are introduced at a low velocity, thereby decreasing the likelihood of the droplets being driven to an undesired region.
  • the pharmaceutical compositions disclosed herein can also be administered to the lungs of a patient via aerosolization, such as with a metered dose inhaler (MDI).
  • MDI metered dose inhaler
  • Metered dose inhalers known in the art can be employed for administration of the claimed pharmaceutical compositions. Breath-activated or breath-actuated MDIs and pressurized MDIs (pMDIs), as well as those comprising other types of improvements which have been, or will be, developed are also compatible with the formulations of the present disclosure and, as such, are contemplated as being within the scope thereof. Propellant-based systems may use suitable pressurized metered- dose inhalers (pMDIs). [0106] Dry powders can use dry powder inhaler devices (DPIs), which are capable of dispersing the drug substance effectively. Dry powder inhaler devices can use a variety of dosage containers (e.g., capsule, blister pack, blister strip, reservoir, cartridge).
  • DPIs dry powder inhaler devices
  • DPIs dry powder inhalers
  • dry powder formulations of the pharmaceutical compositions described herein may be formulated for characteristics at particulate and bulk level to ensure the drug delivery to lower airway regions.
  • the DPI are pre-filled with doses of the pharmaceutical composition.
  • the DPI are pre-filled with a single dose.
  • the DPI are pre-filled with multiple doses.
  • the DPI is disposable after usage.
  • the DPI or aerosolized device does not contain a capsule for the pharmaceutical composition, while the device itself has a compartment or compartments for filling and/or refilling of the pharmaceutical composition.
  • the DPI uses a capsule comprising the pharmaceutical composition.
  • the DPI or aerosolization device requires inhalation of the patient to aerosolize the pharmaceutical composition.
  • the DPI is a single-dose DPI or a multi-dose DPI.
  • the DPI is a reusable DPI or a non-reusable DPI.
  • dry powder formulations can blend micronized drug particles (less than 5 micron in size) with larger carrier particles to address flowability and dose variability issues.
  • the concentration of drug in drug-carrier dry powder formulations is low (e.g., 1 drug.: 67.5 carrier). In some embodiments, the concentration of drug in drug- carrier dry powder formulations vary depending on the aerosol dispersion properties of the formulation. Therefore, during drug-carrier mixing, drug particles will preferably adhere to the active binding sites (more adhesive areas) on the carrier surface and expected to separate from carrier surface upon inhalation. Drug re-dispersion is considered most important for getting drug particles into deep lung airway regions. Usually, only small amounts of drug reach the lower airway regions due to strong drug-carrier adhesion. Indeed, drug re-dispersion is a function of balance between cohesive forces (between the drug particles) and the adhesive forces (between drug and carrier particles).
  • a nebulizer may be used to deliver the pharmaceutical composition in an acute care setting for a short period (7 or less days). In some cases, a nebulizer may be used to deliver the pharmaceutical composition as an adjunct therapy to standard of care antibiotics. In some cases, a nebulizer may be used to deliver the pharmaceutical composition to rapidly reduce bacterial burden in the lung in recurrent acute and chronic lung infections in individuals with cystic fibrosis.
  • the distribution of aerosol droplet of a liquid pharmaceutical composition described herein or a particle of a dry powder pharmaceutical composition as described herein of an inhalable can be expressed in terms of either: the mass median aerodynamic diameter (MMAD) — the size at which half of the mass of the aerosol is contained in smaller droplets and half in larger droplets; volumetric mean diameter (VMD); mass median diameter (MMD); the fine droplet fraction (FDF) or the fine particle fraction (FPF) - the percentage of droplets/particle that are ⁇ 5 um in diameter.
  • MMAD mass median aerodynamic diameter
  • VMD volumetric mean diameter
  • MMD mass median diameter
  • FDF fine droplet fraction
  • FPF fine particle fraction
  • the higher the fine droplet fraction or fine particle fraction the higher the proportion of the emitted dose that is to deposit the lung.
  • Inhaled droplets/particles are subject to deposition by one of two mechanisms: impaction, which usually predominates for larger droplets/particles, and sedimentation, which is prevalent for smaller droplets/particles. Impaction occurs when the momentum of an inhaled droplet/particle is large enough that the droplet/particle does not follow the air stream and encounters a physiological surface. In contrast, sedimentation occurs primarily in the deep lung when very small droplets/particles which have traveled with the inhaled air stream encounter physiological surfaces as a result of random diffusion within the air stream.
  • Pulmonary drug delivery can be accomplished by inhalation of an aerosol through the mouth and throat.
  • Droplets having a mass median aerodynamic diameter (MMAD) of greater than about 5 microns generally do not reach the lung; instead, they tend to impact the back of the throat and are swallowed and possibly orally absorbed.
  • Droplets/particles having diameters of about 1 to about 5 microns are small enough to reach the upper-to-mid-pulmonary region (conducting airways) but may be too large to reach the alveoli.
  • VMD volumetric mean diameter
  • MMD mass median diameter
  • MMAD mass median diameter
  • droplet/particle size or aerosolized pharmaceutical composition described herein has a MMAD of about 1 ⁇ m to about 5 ⁇ m.
  • droplet/particle size or aerosolized pharmaceutical composition described herein has a MMAD of about 1 ⁇ m, 1.5 ⁇ m, 2.0 ⁇ m, 2.5 ⁇ m, 3.0 ⁇ m, 3.5 ⁇ m, 4.0 ⁇ m, 4.5 ⁇ m, or about 5 ⁇ m.
  • the nebulizer generates an average droplet size of about 1 ⁇ m, 1.5 ⁇ m, 2.0 ⁇ m, 2.5 ⁇ m, 3.0 ⁇ m, 3.5 ⁇ m, 4.0 ⁇ m, 4.5 ⁇ m, or about 5 ⁇ m MMAD.
  • the DPI generates an average particle size of about 1 ⁇ m, 1.5 ⁇ m, 2.0 ⁇ m, 2.5 ⁇ m, 3.0 ⁇ m, 3.5 ⁇ m, 4.0 ⁇ m, 4.5 ⁇ m, or about 5 ⁇ m MMAD.
  • the moisture content is typically less than about 15 wt %, such as less than about 10 wt %, less than about 5 wt %, less than about 2 wt %, less than about 1 wt %, or less than about 0.5 wt %.
  • the nebulizer / DPI generates an average flow rate of 0.4 mL/min.
  • the nebulizer / DPI generates an average flow rate of 0.5 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.6 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.7 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.8 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.9 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 1.0 mL/min.
  • the nebulizer generates an average flow rate of 1.1 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 1.2 mL/min.
  • Biofilm [0115] A microbial film can refer to a consortium comprising microorganisms and extracellular material. In some cases, microorganisms may comprise one or more pathogenic bacteria that can harm a host organism In some cases the one or more pathogenic bacteria may excrete various chemicals including polysaccharides and proteins, which can form an extracellular matrix.
  • the extracellular matrix can provide a stabilizing and protective layer for the one or more pathogenic bacteria, such that the one or more pathogenic bacteria within the extracellular matrix exhibit a much higher resistance to antibiotics than the one or more pathogenic bacteria would exhibit in the absence of the extracellular matrix.
  • a biofilm may reduce the overall metabolic rate of bacteria, which may contribute to the increased resistance of pathogenic bacteria to the one or more antibiotics.
  • a microbial film can develop on various surfaces of a host organism. Depending on the locus of an initial infection with one or more pathogenic bacteria, a microbial film may develop over time as the pathogenic bacteria grow in number and excrete the various chemicals.
  • an infection may spread from the locus of the initial infection to other areas of the host organism.
  • a microbial film may develop on a surface of in the respiratory tract of a human being.
  • the surface may be within a nasal cavity, an oral cavity, a pharynx, a larynx, a trachea, a bronchus, a bronchi, a alveoli, or a lung.
  • the surface may form a structure or a substructure of any of the aforementioned organs and tissues.
  • a microbial film may develop on various surfaces of a medical device.
  • a patient in intensive care may sometimes be given tracheal intubation to assist the patient’s breathing.
  • Bacteria on an intubation device may enter the respiratory of the tract, and lead to an infection.
  • a patient may be provided a ventilator in certain hospital settings or in certain medical procedure. Bacteria on the ventilator may enter the respiratory tract and lead to an infection. In some cases, the infection may lead to pneumonia.
  • Various medical devices may lead to an infection of the respiratory of a human being.
  • the medical device may be used to assist in breathing.
  • the medical device may be used for diagnostics.
  • the medical device may be a suction device.
  • the medical device may be a tube that is configured to be inserted into at least a portion of the human being’s respiratory system.
  • the medical device may be an inhaler.
  • the medical device may be a bronchoscopy endoscope, a tracheostomy tube, a spirometer, a positive airway pressure system, or a laryngectomy tube.
  • it may be desirable to prevent a respiratory infection in a human being with a prophylactic treatment of the human being’s respiratory tract.
  • a patient may be prophylactically treated with a method of the present disclosure to prevent an infection.
  • a patient may be prophylactically treated with a pharmaceutical composition of the present disclosure to prevent an infection.
  • a patient may be prophylactically treated with a system of the present disclosure to prevent an infection [0121]
  • the infection may be treated with a method of the present disclosure.
  • the infection may be treated with a pharmaceutical composition of the present disclosure.
  • the infection may be treated with a system of the present disclosure.
  • a respiratory infection in a human being may be treated with a method of the present disclosure.
  • the infection may be treated with a pharmaceutical composition of the present disclosure.
  • the infection may be treated with a system of the present disclosure.
  • a human being may be vulnerable to a respiratory bacterial infection.
  • a human being may be immunocompromised.
  • a human being may have neutropenia.
  • a human being may be HIV positive. In some cases, a human being may be of an old age, wherein old age may be defined as greater than 60 years old. In some cases, a human being may be of a young age, wherein young age may be defined as less than 10 years old. In some cases, a human being may be undergoing another medical treatment, such as chemotherapy. In some cases, a human being may have a lung disease. In some cases, a human being may have a genetic disease. In some cases, a human being may have cystic fibrosis. Inhibition of Respiratory Inflammatory Response [0124] Inflammation response, in some cases, is a result of a natural defensive mechanism of an organism.
  • an organism may respond to an irritant (which can be both drugs or pathogens) by increasing blood flow to an area, which can result in redness, increase in temperature, or an increase in swelling at the location of the irritant.
  • an irritant which can be both drugs or pathogens
  • immune cells of the organisms may concentrate at the location of the irritant.
  • immune cells of the organisms may release inflammatory mediators, for example, hormones.
  • hormones may include bradykinin and/or histamine.
  • Examples of medical conditions that have acute respiratory inflammation effects include pneumonia and acute respiratory distress syndrome
  • Examples of medical conditions that have chronic respiratory inflammation effects include asthma and chronic obstructive pulmonary disease.
  • a lung as a vital organ in the exchange of gases between the human body and the atmosphere, left untreated in the event of acute inflammation or in a period of chronic inflammation can lead to further medical complications that range from mild to life-threatening in magnitude.
  • inflammation within the respiratory system can lead to necrosis of tissue associated with the respiratory system.
  • inflammation can lead to mortality in patients.
  • inflammation may be associated or correlated to levels of certain inflammatory biochemical markers.
  • the inflammatory biochemical markers may comprise tumor necrosis factor alpha (TNF- ⁇ ) and/or interleukin-6.
  • the inflammatory biochemical markers may comprise a cytokine.
  • the inflammatory biochemical markers may comprise interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-11, interleukin-12, interleukin-13, interleukin-14, interleukin-15, interleukin-16, interleukin-17, interleukin-18, interleukin-19, interleukin-20, interleukin-21, interleukin-22, interleukin-23, interleukin-24, interleukin-25, interleukin-26, interleukin-27, interleukin-28, interleukin-29, interleukin-30, interleukin-31, interleukin-32, interleukin-33, interleukin-34, interleukin-35, or interleukin
  • the inflammatory biochemical markers may comprise a chemokine, an interferon, or a lymphokine.
  • a pharmaceutical composition of the present disclosure upon administration to at least a portion of a respiratory tract, may inhibit an inflammation response.
  • a pharmaceutical composition of the present disclosure upon administration to at least a portion of a respiratory tract, may inhibit the levels of one or more inflammatory biochemical markers.
  • a pharmaceutical composition of the present disclosure upon administration to at least a portion of a respiratory tract, may comprise inhibiting the levels of tumor necrosis factor alpha (TNF- ⁇ ) and/or interleukin-6.
  • a pharmaceutical composition of the present disclosure upon administration to at least a portion of a respiratory tract, may reduce the rise in an inflammation response. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may reduce the rise in the levels of one or more inflammatory biochemical markers. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may reduce the rise in the levels of tumor necrosis factor alpha (TNF- ⁇ ) and/or interleukin-6.
  • TNF- ⁇ tumor necrosis factor alpha
  • a method present disclosure may inhibit an inflammation response. In some cases, a method present disclosure may inhibit the levels of one or more inflammatory biochemical markers.
  • a method present disclosure may inhibit the levels of tumor necrosis factor alpha (TNF- ⁇ ) and/or interleukin-6.
  • a method present disclosure may reduce the rise in an inflammation response.
  • a method present disclosure may reduce the rise in the levels of one or more inflammatory biochemical markers.
  • a method present disclosure may reduce the rise in the levels of tumor necrosis factor alpha (TNF- ⁇ ) and/or interleukin-6.
  • DOSAGE [0131]
  • the pharmaceutical formulations described herein is in the form of a unit dose.
  • a pharmaceutical formulation can be formulated to optimize pharmacokinetics/pharmacodynamics of a peptide or salt thereof contained therein.
  • a peptide, pharmaceutically acceptable salt thereof, or pharmaceutical formulation comprising a peptide or salt thereof described herein can be administered at a dose of from about 1 mg to about 1000 mg, from about 5 mg to about 1000 mg, from about 10 mg to about 1000 mg, from about 15 mg to about 1000 mg, from about 20 mg to about 1000 mg, from about 25 mg to about 1000 mg, from about 30 mg to about 1000 mg, from about 35 mg to about 1000 mg, from about 40 mg to about 1000 mg, from about 45 mg to about 1000 mg, from about 50 mg to about 1000 mg, from about 55 mg to about 1000 mg, from about 60 mg to about 1000 mg, from about 65 mg to about 1000 mg, from about 70 mg to about 1000 mg, from about 75 mg to about 1000 mg, from about 80 mg to about 1000 mg, from about 85 mg to about 1000 mg, from about 90 mg to about 1000 mg, from about 95 mg to about 1000 mg, from about 100 mg to about 1000 mg, from about 150 mg to about 1000 mg, from about 200 mg to about 1000 mg, from about 250
  • a peptide, pharmaceutically acceptable salt thereof, or pharmaceutical formulation comprising a peptide or salt thereof described herein can be administered at a dose of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 100 101 102 103 104 105 106 107
  • effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection can be a concentration from at least about 0.01 ⁇ g/mL to at least about 100 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 1 mg/mL to at least about 10 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 0.1 mg/mL to at least about 10 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 1 mg/mL to at least about 100 mg/mL.
  • effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 0.1 mg/mL to at least about 100 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about at least about 0.5 mg/mL to at least about 1 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration about 1 mg/mL.
  • effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration about 10 mg/mL.
  • pharmaceutical formulation comprising a peptide or pharmaceutically acceptable salt is present at a concentration from at least about 0.01 ⁇ g/mL to at least about 100 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt is present at a concentration from at least about at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt is present at a concentration from at least about at least about 0.5 mg/mL to at least about 1 mg/mL.
  • the peptide or pharmaceutically acceptable salt is present at a concentration about 1 mg/mL.
  • pharmaceutical formulation comprising a peptide or pharmaceutically acceptable salt can exhibit antimicrobial activity against an infection at a concentration from at least about 0.01 ⁇ g/mL to at least about 0.02 ⁇ g/mL, from at least about 0.02 ⁇ g/mL to at least about 0.03 ⁇ g/mL, from at least about 0.03 ⁇ g/mL to at least about 0.04 ⁇ g/mL, from at least about 0.04 ⁇ g/mL to at least about 0.05 ⁇ g/mL, from at least about 0.05 ⁇ g/mL to at least about 0.06 ⁇ g/mL, from at least about 0.06 ⁇ g/mL to at least about 0.07 ⁇ g/mL, from at least about 0.07 ⁇ g/mL to at least about 0.08 ⁇ g/mL, from at least about 0.08 ⁇ g/mL to at least about 0..
  • effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection may be a concentration from at least about 0.01 ⁇ g/mL to at least about 0.02 ⁇ g/mL, from at least about 0.02 ⁇ g/mL to at least about 0.03 ⁇ g/mL, from at least about 0.03 ⁇ g/mL to at least about 0.04 ⁇ g/mL, from at least about 0.04 ⁇ g/mL to at least about 0.05 ⁇ g/mL, from at least about 0.05 ⁇ g/mL to at least about 0.06 ⁇ g/mL, from at least about 0.06 ⁇ g/mL to at least about 0.07 ⁇ g/mL, from at least about 0.07 ⁇ g/mL to at least about 0.08 ⁇ g/mL, from at least about 0.08 ⁇ g/mL to at least about 0.09 ⁇ g/mL, from at least about 0.09 ⁇ g/mL to at least about 0.1 ⁇ g
  • effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection may be from at least about 1 ⁇ L to at least about 2 ⁇ L, from at least about 2 ⁇ L to at least about 3 ⁇ L, from at least about 3 ⁇ L to at least about 4 ⁇ L, from at least about 4 ⁇ L to at least about 5 ⁇ L, from at least about 5 ⁇ L to at least about 6 ⁇ L, from at least about 6 ⁇ L to at least about 7 ⁇ L, from at least about 7 ⁇ L to at least about 8 ⁇ L, from at least about 8 ⁇ L to at least about 9 ⁇ L, from at least about 9 ⁇ L to at least about 10 ⁇ L, from at least about 10 ⁇ L to at least about 20 ⁇ L, from at least about 20 ⁇ L to at least about 30 ⁇ L, from at least about 30 ⁇ L to at least about 40 ⁇ L, from at least about 40 ⁇ L to at least about 50 ⁇ L, from at least about
  • kits can comprise a pharmaceutical composition comprising a peptide, or pharmaceutically acceptable salt thereof, and an excipient.
  • a method can further comprise an inclusion of instructions for use.
  • instructions for use can direct administration of a unit dose of a pharmaceutical composition to a subject.
  • the kits include separate containers/receptacles for containing the pharmaceutical composition as described herein.
  • the kits include a single container for containing the pharmaceutical composition.
  • kits can further include instructions for methods of using the kit
  • the instructions for use of the kit can comprise instructions for use of the pharmaceutical composition and the aerosolization device (e.g., a nebulizer, dry powder inhaler, aerosolization device) to treat or prevent lung disease or injury.
  • the kit disclosed herein comprises a pharmaceutical composition disclosed herein.
  • the pharmaceutical composition of the kit disclosed herein further comprises an excipient, pH buffering or adjusting agent.
  • the kit comprises a pharmaceutical composition that is a dry powder.
  • the kit comprises a pharmaceutical composition that is a liquid.
  • the kit comprises a pharmaceutical composition that is an aerosol.
  • the kit comprises a pharmaceutical composition whose pH is between 4.5 and 6.5. In some embodiments, the kit comprises a pharmaceutical composition whose osmolality is between at least 270 mOsm/kg to at least 350 mOsm/kg. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is acetate. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is mannitol. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is trehalose. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is human serum albumin. In some embodiments, the pharmaceutical composition of the kit comprises an antibiotic.
  • the pharmaceutical composition of the kit comprises a neutrophil elastase. In some embodiments, the pharmaceutical composition of the kit comprises a lung surfactant.
  • An inhaler kit can comprise a pharmaceutical composition comprising a peptide disclosed herein or a pharmaceutically acceptable salt thereof and an excipient. A method can further comprise an inclusion of instructions for use. In some embodiments, instructions for use can direct administration of a unit dose of a pharmaceutical composition to a subject.
  • the inhaler kits include separate containers/receptacles for containing the pharmaceutical composition as described herein. In some other cases, the inhaler kits include a single container for containing the pharmaceutical composition.
  • the inhaler kits can further include instructions for methods of using the inhaler kit.
  • the instructions for use of the inhaler kit can comprise instructions for use of the pharmaceutical composition and the aerosolization device (e.g., a nebulizer, dry powder inhaler, aerosolization device) to treat or prevent lung disease or injury.
  • the inhaler kit disclosed herein comprises a pharmaceutical composition disclosed herein.
  • the pharmaceutical composition disclosed herein further comprises an excipient, pH buffering or adjusting agent.
  • the inhaler kit comprises a pharmaceutical composition that is a dry powder.
  • the inhaler kit comprises a pharmaceutical composition that is a liquid.
  • the inhaler kit comprises a pharmaceutical composition that is an aerosol.
  • the inhaler kit comprises a pharmaceutical composition whose pH is between 4.5 and 6.5. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose osmolality is between at least 270 mOsm/kg to at least 350 mOsm/kg. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is acetate. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is mannitol. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is trehalose. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is human serum albumin.
  • the pharmaceutical composition of the inhaler kit comprises an antibiotic. In some embodiments, the pharmaceutical composition of the inhaler kit comprises a neutrophil elastase. In some embodiments, the pharmaceutical composition of the inhaler kit comprises a lung surfactant. TERMINOLOGY [0140] As used herein, the term “about” or “approximately” can mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean plus or minus 10%, per the practice in the art.
  • “about” can mean a range of plus or minus 20%, plus or minus 10%, plus or minus 5%, or plus or minus 1% of a given value.
  • the term can mean within an order of magnitude, within 5-fold, or within 2-fold, of a value.
  • biofilm As used herein, the terms “biofilm”, “microbial film”, “microbial biofilm”, “bacterial film”, refers to any film comprising microorganisms and their excretions. [0143] As used herein, the terms “comprising,” “comprise” or “comprised,” and variations thereof in reference to elements of an item formulation apparatus method process system claim etc. are intended to be open-ended, meaning that the item, formulation, apparatus, method, process, system, claim etc. includes those elements and other elements can be included and still fall within the scope/definition of the described item, formulation, apparatus, method, process, system, claim etc. As used herein, "a” or “an” means one or more. As used herein "another" may mean at least a second or more.
  • the term “object” refers to any object with a surface. Some embodiments in the present disclosure may be applied to the surface of an object to prevent or to treat microbial biofilm.
  • the object can a solid object, a liquid object, a hard object, a soft object, a metallic object, a polymeric object, a ceramic object, a composite object, a biological object, members of the animal kingdom, a human being, a biological transplant object, a replaced joint, or any other object with a surface on which some of the disclosed methods and the formulations can be applied.
  • the terms "patient” or “subject” generally refer to any individual that has, may have, or may be suspected of having a disease condition (e.g., a bacterial infection).
  • the bacterial infection may be caused by surgeries, physical wounds, etc.
  • the subject may be an animal.
  • the animal can be a mammal, such as a human, non-human primate, a rodent such as a mouse or rat, a dog, a cat, pig, sheep, or rabbit. Animals can be fish, reptiles, or others. Animals can be neonatal, infant, adolescent, or adult animals.
  • the subject may be a living organism.
  • the subject may be a human.
  • Humans can be greater than or equal to 1, 2, 5, 10, 20, 30, 40, 50, 60, 65, 70, 75, 80 or more years of age.
  • a human may be from about 18 to about 90 years of age.
  • a human may be from about 18 to about 30 years of age.
  • a human may be from about 30 to about 50 years of age.
  • a human may be from about 50 to about 90 years of age.
  • the subject may have one or more risk factors of a condition and be asymptomatic.
  • the subject may be asymptomatic of a condition.
  • the subject may have one or more risk factors for a condition.
  • the subject may be symptomatic for a condition.
  • the subject may be symptomatic for a condition and have one or more risk factors of the condition.
  • the subject may have or be suspected of having a disease, such as an infection.
  • the subject may be a patient being treated for a disease, such as an infection.
  • the subject may be predisposed to a risk of developing a disease such as a bacterial infection.
  • the subject may be in remission from a disease, such as a bacterial infection.
  • the subject may not have a bacterial infection.
  • the subject may be healthy.
  • a “pharmaceutically acceptable excipient”, “aqueous carrier” or “pharmaceutically acceptable aqueous carrier” refer to solvents or dispersion media, and the like, that are physiologically compatible and known to those skilled in the art.
  • Examples of pharmaceutically acceptable carriers include one or more of water, saline, phosphate buffered saline dextrose glycerol ethanol and the like as well as combinations thereof Pharmaceutically acceptable carriers may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the active agent.
  • auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the active agent.
  • Tween® 80 refers to polysorbate 80 or polyethylene glycol sorbitan monooleate.
  • a “effective amount” of an active agent can refer to an amount that is effective to achieve a desired result.
  • an effective amount of a given active agent can vary with respect to factors such as the type and severity of the disorder or disease being treated and the age, gender, and weight of the patient.
  • the term “homology” can refer to a % identity of a polypeptide to a reference polypeptide.
  • any particular polypeptide can be at least 50%, 60%, 70%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to any reference amino acid sequence of any polypeptide described herein (which may correspond with a particular nucleic acid sequence described herein), such particular polypeptide sequence can be determined conventionally using known computer programs such the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis.53711).
  • the parameters can be set such that the percentage of identity is calculated over the full length of the reference amino acid sequence and that gaps in homology of up to 5% of the total number of amino acid residues in the reference sequence are allowed.
  • identity between a reference sequence query sequence, i.e., a sequence of the present invention
  • subject sequence also referred to as a global sequence alignment
  • the identity between a reference sequence and a subject sequence may be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci.6:237-245 (1990)).
  • the percent identity can be corrected by calculating the number of residues of the query sequence that are lateral to the N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence.
  • a determination of whether a residue is matched/aligned can be determined by results of the FASTDB sequence alignment. This percentage can be then subtracted from the percent identity, calculated by the FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score can be used for the purposes of this embodiment. In some embodiments, only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence are considered for this manual correction. For example, a 90 amino acid residue subject sequence can be aligned with a 100 residue query sequence to determine percent identity.
  • the deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus.
  • the 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%.
  • a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query.
  • co-administration can encompass administration of selected therapeutic agents to a subject, and can include treatment regimens in which agents are administered by the same or different route of administration or at the same or different times.
  • a peptide disclosed herein can be co-administered with other agents.
  • a peptide and an additional agent(s) can be administered in a single formulation.
  • a peptide and an additional agent(s) can be admixed in the formulation.
  • a same peptide or agent can be administered via a combination of different routes of administration.
  • each agent administered can be in a therapeutically effective amount.
  • Example 1 SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination in the presence and absence of neutrophil elastase
  • This example illustrates the determination of the in vitro activity of eCAPs, SEQ ID NO: 17 and SEQ ID NO: 1, compared to other antimicrobial agents in the presence of neutrophil elastase against contemporary, clinically relevant respiratory bacteria, including MDR and XDR strains and isolates of P. aeruginosa, S.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the presence of neutrophil elastase against contemporary, clinically relevant respiratory bacteria from patients with CF.
  • HNE Human neutrophil elastase
  • Elastin Products Company Owensville, MO
  • neutrophil elastase-specific chromogenic substrate Elastin Products Company, Owensville, MO
  • DNase Pulmozyme
  • CAMHB neutrophil elastase-specific chromogenic substrate
  • RPMI-1640 RPMI-1640
  • 0002% P-80 Amresco
  • SEQ ID NO: 17 and SEQ ID NO: 1 will be freshly prepared at 20x, 0.64 mg/mL, in DPBS containing 0.002% P-80.
  • the 11-point dilutions of SEQ ID NO: 17 and SEQ ID NO: 1 will be carried out using DPBS with 0.002% P- 80.
  • the P. aeruginosa and S. aureus strains for MIC testing of this study will be obtained from the American Type Culture Collection (ATCC; S. aureus ATCC 29213) and the FDA CDC AR Isolate Bank (P. Aeruginosa AR-BANK#0246 and P. aeruginosa AR-BANK#0266). Susceptibility is summarized in Table 2 and will be determined following the Clinical Laboratory Standards Institute (CLSI) M07-A10 microdilution procedure and the CLSI M100 interpretive criteria. The species identity was confirmed with 16S analysis.
  • the antimicrobial resistance genes of each strain, Table 1 were provided by the AR Isolate bank website and were identified from whole genome sequence analysis using the ResFinder tool.
  • Table 2 P. aeruginosa and S. aureus strains for MIC studies, antibiotic susceptibility. S denotes susceptible, R denotes resistant or not susceptible, and I denotes intermediate susceptibility based on the CLSI interpretive criteria published in CLSI M100. Colistin susceptibility is based on EUCAST breakpoints. Asterisk (*) denotes that P. aeruginosa strain ATCC 27853 will be used as the quality control strain for MIC assay.
  • Plates 3 and 4 will be created to be identical to Plates 1 and 2 but will also receive 75 ⁇ L of a neutrophil elastase- specific chromogenic substrate, which comprises 0.8 mM methoxysuccinyl-AAPV-P- nitroanalide in 0.1 M Tris-HCl (tris[hydroxymethyl] aminomethane–hydrochloride)/0.15 M sodium chloride (NaCl) (pH 7.5). After both plates are incubated for 1 hour at 37 °C, the reaction will be stopped with 40 ⁇ L of 50 ⁇ M soybean trypsin inhibitor in 0.1 M Tris-HCl/0.15 M NaCl (pH 7.5).
  • a neutrophil elastase- specific chromogenic substrate which comprises 0.8 mM methoxysuccinyl-AAPV-P- nitroanalide in 0.1 M Tris-HCl (tris[hydroxymethyl] aminomethane–hydrochloride)/0.15 M sodium chloride
  • HNE treated SEQ ID NO: 1 or SEQ ID NO: 17 will be utilized as the source of antimicrobial peptide in a broth microdilution MIC assay with cation-adjusted Mueller Hinton broth (CAMHB) or RPMI-1640 as the broth medium. Both media will be supplemented with 0.002% P-80 for testing of SEQ ID NO: 17 and SEQ ID NO: 1.
  • the MIC ⁇ g/mL
  • Appropriate QC antibiotics and strains will be included to validate the assay.
  • SEQ ID NO: 1 and SEQ ID NO: 17 will be incubated with various concentrations of Pulmozyme (0.5 - 16 ⁇ M) and subsequently added to the MIC assay using the P. aeruginosa and S. aureus strains listed in Table 2.
  • the data expected to be obtained will be biological activity (MIC determination) of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of neutrophil elastase.
  • Example 2 SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination in the presence and absence of surfactant
  • This example illustrates the determination of the in vitro activity of eCAPs, SEQ ID NO: 17 and SEQ ID NO: 1, compared to other antimicrobial agents in the presence of surfactant (Survanta®) against contemporary, clinically relevant respiratory bacteria, including MDR and XDR strains and isolates of P. aeruginosa, S. maltophilia, B. cepacia, A.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the presence of surfactant against contemporary, clinically relevant respiratory bacteria from patients with CF.
  • CAMHB cation-adjusted Mueller Hinton broth
  • RPMI RPMI media.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the presence of surfactant against contemporary, clinically relevant respiratory bacteria from patients with CF.
  • SEQ ID NO: 17 and SEQ ID NO: 1 will be tested in an 11-point titration from 0.032 to 32 ⁇ g/mL with and without Survanta® (0, 2.5, 5, and 10%) in RPMI medium. All tests will be performed in duplicate. The method for preparing medium, inoculum and the reading of MIC values will follow the guidelines of CLSI M07-A10 (2020).
  • the direct colony suspension method will be used to prepare inoculated broth. Isolated colonies will be taken from an 18–24 h culture plate and resuspended in 2 mL saline solution (0.9% NaCl) and adjusted to OD620nm 0.085, which is equivalent to 0.5 McFarland standard (OD620nm range 0.085 to 0.088).
  • the bacterial suspension of OD620nm 0.085 corresponds to approximate 1.5 x 10 8 CFU/mL; and will be subsequently diluted to reach the final bacterial count of approximately 5 x 10 5 CFU/mL with a range of 2–8 x 10 5 CFU/mL.
  • SEQ ID NO: 17 and SEQ ID NO: 1 will be tested in an 11-point titration from 0.032 to 32 ⁇ g/mL with 0%, 2.5%, 5% and 10% (v/v) of Survanta® in RPMI medium as described below and shown in FIG.1.
  • Assay plates will be incubated at 37 °C for 18 h. The test plate will be visually examined and each well will be visually scored for growth or complete inhibition of growth then the MIC is recorded. The MIC endpoint is the lowest concentration that results in 100% visual growth inhibition. The duplicate assays may yield the same MIC value. If the values differ, the higher MIC value will be reported.
  • a control compound dilution plate will be included to observe precipitate in the test medium that is not inoculated.
  • the compound dilution will be generated in RPMI with or without Survanta® as the same concentrations as the MIC assay plate.
  • the control plate will be incubated at 37°C for 18 h.
  • the test plate will be visually examined and each well will be visually scored for precipitate with results reported.
  • the data expected to be obtained is the biological activity (MIC determination) of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of surfactant.
  • SEQ ID NO: 17 and SEQ ID NO: 1 The data will be analyzed and interpreted by comparing the MIC of SEQ ID NO: 17 and SEQ ID NO: 1 to the same bacteria in the presence and absence of surfactant.
  • Pseudomonas aeruginosa, methicillin-resistant S. aureus, S. maltophilia, B. cepacia, and A. xylosoxidans are bacteria that can be found in airway secretions of individuals with CF. These bacteria may be multidrug resistant to standard of care antibiotics.
  • the in vitro activity of SEQ ID NO: 17 and SEQ ID NO: 1 and other antimicrobials against these bacteria will be determined in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI 2020).
  • Example 3 SEQ ID NO: 17 and SEQ ID NO: 1 MIC Determination in the presence of CAMHB and RPMI [0169]
  • This example illustrates the determination of the in vivo activity, including respiratory track tolerability / toxicity, toxicokinetics and efficacy, of SEQ ID NO: 17 and SEQ ID NO: 1 in animals.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the standard test medium CAMHB as well as in RPMI medium, which may support better solubility, against contemporary, clinically relevant respiratory bacteria from patients with CF.
  • SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination will be studied for SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination.
  • These bacteria will be reference strains from the American Type Culture Collection (ATCC; Manassas, VA), the Centers for Disease Control Antibiotic Resistance Bank (CDC, Atlanta, GA) and clinical isolates from the Micromyx repository (MMX; Kalamazoo MI) MIC Assay in the presence of CAMHB and RPMI [0171]
  • ATCC American Type Culture Collection
  • CDC Centers for Disease Control Antibiotic Resistance Bank
  • MMX Kalamazoo MI
  • the in vitro activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be determined by broth microdilution MIC testing in CAMHB and RPMI in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI 2020).
  • the comparators will include imipenem, levofloxacin, tigecycline, linezolid, vancomycin, oxacillin, ceftazidime, colistin, and amikacin.
  • Media employed for testing in the broth microdilution MIC assay for all organisms will be cation-adjusted Mueller Hinton broth (MHBII; Becton Dickinson) and RPMI-1640 medium (Hyclone) with MOPS (EMD Millipore). Both media will be supplemented with 0.002% P-80 (Amresco) for testing of SEQ ID NO: 17 and SEQ ID NO: 1.
  • the MIC ( ⁇ g/mL) will be read and recorded as the lowest concentration of drug that inhibits visible growth of the organism.
  • MIC 50/90 values and ranges will be reported, MIC and cumulative distributions of SEQ ID NO: 17 and SEQ ID NO: 1 will be reported against strain and isolates tested. Antibiotic susceptibilities will be interpreted using current CLSI susceptibility breakpoint criteria (M100, 2020).
  • the data expected to be obtained is MIC determination of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of surfactant. The data will be analyzed and interpreted by comparing the MIC of SEQ ID NO: 17 and SEQ ID NO: 1 to the same bacteria in the presence and absence of surfactant. No potential difficulties and/or limitations of the proposed procedure are anticipated to achieve this aim.
  • Example 4 SEQ ID NO: 17 and SEQ ID NO: 1 respiratory track tolerability / toxicity and toxicokinetics in rats
  • the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide
  • the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals.
  • This example illustrates the determination of respiratory tract tolerability / toxicity and toxicokinetics of SEQ ID NO: 17 and SEQ ID NO: 1 in rats. In vitro complex cellular systems will be used to evaluate respiratory track tolerability.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may be tolerable and may have minimal respiratory track toxicity in rats.
  • Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy [0176] Table 3. Study design for an Escalating and 7-Day Range Finding Inhalation Toxicity Study in Rats. Compliance: Non-GLP S D D F D R A I P [0177] Table 4. Test system groups for Example 4.
  • Asterisk denotes that additional animals in Groups 5-8 will be used for Toxicokinetic sample collections. 8 (Repeat Dose) TBD 5+6 5+6 [0178] Table 5. Test system group details for Example 4. S T A Source: Charles River Pretreatment Period: Two weeks D B o F C T C ll t T B T s . ( on ro an g ose) (o er ssues re a ne ).
  • Example 5 SEQ ID NO: 17 and SEQ ID NO: 1 respiratory track tolerability / toxicity and toxicokinetics in monkeys
  • the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide
  • the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals.
  • This example illustrates the determination of respiratory tract tolerability / toxicity and toxicokinetics of SEQ ID NO: 17 and SEQ ID NO: 1 in monkeys.
  • SEQ ID NO: 17 and SEQ ID NO: 1 may be tolerable and may have minimal respiratory track toxicity in monkeys.
  • Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy.
  • Table 6. Study design for an Escalating and 7-Day Range Finding Inhalation Toxicity Study in Monkeys. C li N GLP S D D F D . R A I P .
  • S T otal Population 5/sex on study; 6/sex ordered Age: 2-3 years or 2.5-4 kg on arrival S P D B F C y T C A T T s .
  • Example 6 A Single Dose PK and BALPF Collection Inhalation Toxicity Study in Monkeys [0185] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals.
  • PK pharmacokinetics
  • BALPF bronchoalveolar pulmonary lavage fluid
  • SEQ ID NO: 17 and SEQ ID NO: 1 may show efficacy in a murine lung infection model.
  • Table 12 Study design for a 14-Day Inhalation Toxicity Study in Sprague Dawley Rats Followed by a 28-Day Recovery.
  • Table 13 Test system groups for Example 7.
  • Asterisk (*) denotes 10/sex/Groups 1 to 4 necropsied 24-hours following the last dose, the remaining 5/sex/Groups 1 and 4 (recovery) ne i d 4 k f ll i h l d 4 TBD 10+5 10+5 18 18 [0194] Table 14. Test system group details for Example 7.
  • Example 9 SEQ ID NO: 17 and SEQ ID NO: 1 efficacy in a murine Pseudomonas aeruginosa extended lung infection model - Tolerability/PK Assessment
  • SEQ ID NO: 17 and SEQ ID NO: 1 will be intratracheally (IT) administered with the dose schedule and concentrations indicated in the Table 18 study design and FIG. 2, top panel. Doses will be intratracheally (IT) or subcutaneously (SC) administered twice per day (BID) with 12 h intervals (ql2h) for five consecutive days. Side effects associated with overt toxicity will be monitored 30 minutes after each dose administration. Mortality and body weight will be observed and recorded daily for each treatment day until sacrifice time point. Neutropenic male ICR mice will be used for the tolerability/PK study. The animals will not be infected.
  • Plasma Two bio samples, plasma and BALF, will be collected at up to 8 time points after the last dose administration (after BID ql2h x 5 days), 3 animals per time point. Plasma will be collected at 0.25, 2, 12, 24, 48, 72, 96, 120 hours (h) post-treatment.
  • Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy.
  • the dose concentrations for animal administration are shown in Table 19 for the tolerability/PK study.
  • the SEQ ID NO: 17 and SEQ ID NO: 1 solution will be freshly formulated in DPBS on the first dosing day, and stored at 4°C, protected from light.
  • Dulbecco’s phosphate buffered saline (DPBS) is purchased as 10x stock, and dilution will be conducted with WFI to reach 1x concentration for vehicle in MIC and animal studies. The formulation will be visually inspected to note heterogeneity.
  • Table 18 Study design for tolerability and pharmacokinetics assessment with mice.
  • cyclophosphamide For longer duration observations, more than 3 days, cyclophosphamide (CP) will be administered by additional IP injections to render the animals persistently neutropenic over the five-day duration of study (Gumbo et. al., 2007) and up to 120 h collection time point (Table 2 study design and Figure 2, top panel).
  • the first CP dose 150 mg/kg, will be administered at four days before treatment (Day –4); the second, 100 mg/kg, 24 h before treatment (Day –1) prior to treatment on Day 0, the third and ongoing CP doses will be at 100 mg/kg on Day +1, Day +3, Day +5 and Day +7.
  • test article SEQ ID NO: 17 and SEQ ID NO: 1
  • I intratracheal
  • Animals will be deeply anesthetized with isoflurane (3%-5%). The mouse will be held upright and a 22 G long blunt needle will be directly inserted into the trachea, and then 20 ⁇ L of test article solution will be injected directly into the trachea.
  • mice will be held in the upright position for about 15 seconds and then placed into the cage for recovery. Animals will be observed at 30 min after dosing to detect acute toxicity which will be recorded and reported, if observed. Animals will be humanely euthanized if severe acute toxicity is observed. Side effect examinations [0208] Animals will be observed for the presence of acute toxic symptoms and autonomic effects after 30 minutes of each IT administration. These observations include: gait, posture, ruffled fur, immobility, mucous membrane, salivation, tremors, convulsions, reactivity to handling, respiratory, stool, and mortality. Body weight and mortality will be observed and recorded daily for each treatment day until sacrifice time point.
  • Plasma and BALF collection Two biosamples, plasma and BALF will be collected. The collection time points are at 0.25, 2, 12, 24, 48, 72, 96, 120 hours (h) post-treatment. The collected samples will be frozen and shipped to the bioanalytical CRO to be designated by Peptilogics. [0210] Plasma collection. Terminal blood collection from cardiac puncture will be conducted under CO2 euthanasia. Blood, 0.3-0.4 mL, will be drawn into tubes coated with K2EDTA, mixed gently and kept on ice and centrifuged at 2,500 ⁇ g for 15 minutes at 4°C within 1 hour of collection.
  • the plasma will be harvested and kept frozen at -80°C until further processing.
  • 0.5 mL of PBS will be administered once through a tracheal cannula after which about 0.2 to 0.3 mL of BALF will be obtained.
  • the BALF will be kept on ice and centrifuged at 2,500 ⁇ g for 15 minutes at 4°C within 1 hour of collection. The supernatant will be collected and kept frozen at -80°C.
  • Example 10 SEQ ID NO: 17 and SEQ ID NO: 1 efficacy in a murine Pseudomonas aeruginosa extended lung infection model - Efficacy Assessment: Extended Lung Infection Model [0212] Efficacy analysis will be conducted with neutropenic mice. Animals will be intranasally (IN) infected with pathogen suspension into the lung. Test article, SEQ ID NO: 17 and SEQ ID NO: 1 and amikacin, will be IT and SC administered, respectively, with the dose schedule and concentrations indicated in the Table 19-21 study design and FIG.2 scheme, bottom panel.
  • SEQ ID NO: 17 and SEQ ID NO: 1 will be IT administered first followed by SC administration of amikacin within 5 minutes (no in vitro antagonism has been observed on checkerboard assay between SEQ ID NO: 17 and SEQ ID NO: 1 with amikacin).
  • Doses will be administered twice at 12 h intervals (BID q12h) for five consecutive days starting at 12 h post-infection. Animals will be humanely euthanized at 12, 36 and 120 h after infection. Lung tissue will be recovered, and pathogen burden will be enumerated with the dilution plating technique.
  • Groups 1 to 7 are the bacterial enumeration groups. Animals in Group 1 will be sacrificed at 12 h post infection for initial bacterial counts (baseline group) at the time of the first test article dosage. Vehicle and test articles will be intratracheally (IT) administered twice (BID) daily with a 12 h interval (q12h) starting at 12 h post infection. Amikacin will be SC administered at BID q12h. Animals will be sacrificed at 36 h post-infection for bacterial counts. [0217] Groups 8 to 13 are the survival arm study groups. Animals will be monitored for survival until 120 h (5 days) post-infection.
  • cyclophosphamide will be administered by four IP injections to render the animals persistently neutropenic over the five-day duration of infection (Gumbo et. al., 2007).
  • the first CP dose 150 mg/kg, will be administered at four days before infection (Day –4); the second, 100 mg/kg, 24 h before infection (Day –1) prior to infection on day 0, the third, 100 mg/kg on Day +1, and the fourth 100 mg/kg on Day +3.
  • mice for infection studies are housed in an A-BSL2 vivarium. Cages for mice are 39 ⁇ 20 ⁇ 16 cm and house up to five animals each. During infection studies, animals are housed in a separate room in negative pressure individually ventilated cages (GM500 IVC seal safe plus cage system; Tecniplast, Italy). All animal rooms are maintained at a temperature range of 20-24°C and humidity between 30-70%, with 12-hour light/dark cycles. These parameters are manually checked twice per day and continuously remotely monitored. Animals have free access to a sterilized standard lab diet [MFG (Oriental Yeast Co., Ltd., Japan)] and autoclaved tap water.
  • MFG sterilized standard lab diet
  • Cage-front checks are performed once per day to assure sufficient food and water, dry bedding, normal animal health and behavior and to identify moribund animals. Cages are supplied with sterile aspen chip bedding as well as autoclaved bricks or plastic tunnels for enrichment per our IACUC policy. Cages are changed twice per week and replaced with freshly autoclaved cages, bedding, enrichment, water and food. [0225] Upon receipt, animals will be evaluated with a basic health examination, including appearance, coat, extremities and orifices. Discovery of wounds, hair loss, unkempt appearance, diarrhea or trauma disqualifies the health certification, and disqualified animals will be humanely euthanized according to the “Euthanasia Working Instruction” (SOP: QWCN38).
  • the criteria include the inability to eat and/or drink, inability to thermoregulate, weight loss (>20%), moribundity, prolonged bleeding, seizures, paralysis, and pain level reaching category E. Animals will be humanely euthanized if any of these criteria are met. [0227] Euthanasia will be performed following the Pharmacology Discovery Services IACUC approved SOP “Euthanasia Working Instruction” (SOP: QWCN38), which follows the 2020 AVMA Guidelines on Euthanasia. Animals will be euthanized using compressed CO2 gas in a CO 2 gas chamber. Mice will be placed into the chamber without crowding them. CO 2 will be allowed to enter the chamber at a flow rate that will displace at least 20% of the chamber volume per minute.
  • PDS complies with the International Guiding Principles for Biomedical Research (CIOMS) and has an IACUC that operates in accordance with “Regulation for Establishing the Committee of Care and Use of Laboratory Animals”. PDS facility and PDS procedures have been fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) in 2014, 2017 and 2020 (#001553).
  • PDS have a current Foreign Assurance from the Office of Laboratory Animal Welfare (F16-00213, legacy #A5890-01), issued by the PHS/NIH for vertebrate animal studies.
  • the mouse lung infection model with neutropenic mice is chosen because of the extensive prior work, including publication and acceptance by the scientific community for assessments of antimicrobial efficacy, drug tolerability and pharmacokinetics.
  • Mouse is the lowest reliable and relevant mammalian species to test agents for safety, pharmacokinetics and efficacy.
  • Non-animal models cannot be used for this research because the analysis depends on the interaction of pathogen growth in mammalian tissue and the exposure of the drug to the infection site, which is a feature of distribution and elimination by organ systems.
  • One mL of the 6-hour culture will be used to seed 99 mL TSB and incubated at 35 – 370C with shaking at 250 rpm for 16 hours.
  • a 20 mL of the 100 mL bacterial culture will be pelleted by centrifugation (3,500 x g) for 15 minutes, then re-suspended in 10 mL cold PBS.
  • the suspension will be diluted, and the optical density measurements will be used to calculate the CFU count of the suspension and to guide further dilutions to achieve the target inoculum of 3 ⁇ 103 CFU/mouse for P. aeruginosa AR-BANK#0266.
  • the PBS suspensions will be stored on ice for no more than one hour prior to animal inoculation. Bacterial count in the challenge organism suspension will be enumerated by dilution plating to suitable plates followed by 20-24 h incubation at 35-37 °C. Challenge [0233] On Day 0, animals will be deeply anesthetized with etomidate-lipuro emulsion ( ⁇ 20 mg/kg, IV). The mouse will be held upright and then drops of bacterial suspension will be gradually released into the nares using a micropipette. A total volume of 20 ⁇ L will be administered, 10 ⁇ L per nostril. The mouse will be held in an upright position for a couple of minutes until the breath returned to a normal rate and depth.
  • test articles SEQ ID NO: 17 and SEQ ID NO: 1
  • Animals will be deeply anesthetized with isoflurane (3%-5%).
  • the mouse will be held upright, and a 22 G long blunt needle will be directly inserted into the trachea, and then 20 ⁇ L of test article solution will be injected directly into the trachea.
  • the mouse will be held in the upright position for about 15 seconds and then placed into the cage for recovery. Animals will be observed at 30 min after dosing to detect acute toxicity which will be recorded and reported, if observed.
  • tissue weight and bacterial counts in each tissue homogenate dilution For each tissue, the homogenate dilution that yielded the largest number of colonies, between 10 to 300 colonies per plate, will be selected to calculate the bacterial counts per gram of tissue (CFU/g). Bacterial counts per gram of tissue (CFU/g) will be tabulated and plotted in GraphPad Prism. The raw colony count data of the homogenate dilutions will be inspected for proportionality within the dilution series.
  • the 10-fold serial dilutions are expected to show 10-fold reductions in counts.
  • Disproportionate data such as fewer counts in the undiluted homogenate samples compared to the diluted sample, would indicate inhibition of colony growth due to drug carry over from the tissue to the test plate. Aberrant titration data would be reported, if observed.
  • Data will be plotted in GraphPad Prism as the bacterial counts per gram tissue of control and treatment groups. The difference in bacterial density between the baseline group (12 h initial counts) and the treatment group will be calculated. Significance will be assessed with ANOVA analysis using GraphPad Prism software.
  • Aerosol formulations of SEQ ID NO: 1 were prepared via combining test peptides disclosed herein with 50 mL of 0.9 % w/v saline buffer or 0.05 M pH 5 acetate buffer, adjusting pH of the resulting solution to pH of 5 via addition of 1N acetic acid or sodium hydroxide, and adjusting osmolality via addition of sodium chloride to 300 mOsm/kg.
  • SEQ ID NO: 1 Formulations 1-12, as well as data for pH, appearance, and osmolality under two physical conditions; one experiment at 5 o C and the other at 40 o C and 75 % relative humidity. The pH, appearance, and stability were measured after one month and after three months under both conditions. SEQ ID NO: 1 was tested at concentrations of 1 mg/mL and 10 mg/mL. [0244] The formulations of SEQ ID NO: 1 aerosol with the excipients tested showed neither higher temperature nor higher SEQ ID NO: 1 concentration significantly affected the pH of the formulations tested aside from the Polysorbate 80 (PS80) excipient.
  • PS80 Polysorbate 80
  • Table 23 shows the aggregation data for the SEQ ID NO: 1 formulations. The analysis was done upon sample preparation, at 1 month, and at 3 months as well as data for storage at 5 o C and at 40 o C and 75 % relative humidity via size exclusion chromatography (SEC). When test article SEQ ID NO: 1 was examined with a variety of excipients, the formulations did not form aggregates under conditions tested and demonstrated a clear, colorless appearance. Neither higher temperature nor higher SEQ ID NO: 1 concentration significantly affected the aggregation of particles. [0246] Table 22. Appearance, pH, and osmolality results of SEQ ID NO: 1 aerosol formulations. , T , H F C F C Formulation, visible visible visible 100 mg/mL particulates particulates particulates
  • Table 24 shows the LC-MS results for the control formulations without excipient. There is virtually no decomposition of SEQ ID NO: 1 within this aerosol formulation over time or at higher temperature and humidity.
  • Table 25 shows the results of Formulation 3 and Formulation 4, which have 0.05M acetate as the buffer. Acetate did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity. This shows 0.05M acetate is a viable excipient to store SEQ ID NO: 1 in aerosol form over time.
  • Table 26 shows the results of Formulation 5 and Formulation 6, which have 1% (w/w) D-mannitol as the excipient. D-mannitol did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity. This shows 1% (w/w) D- mannitol is a viable excipient to administer SEQ ID NO: 1 in aerosol form.
  • Table 27 shows the results of Formulation 7 and Formulation 8, which have 1% (w/w) D-trehalose as the excipient. D-trehalose did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity.
  • Table 28 shows the results of Formulation 9 and Formulation 10, which have 0.05% (w/w) polysorbate 80 (PS80) as the excipient.
  • PS80 significantly increased decomposition of 1.0 mg/mL aerosol SEQ ID NO: 1 at elevated temperature and humidity. This shows that SEQ ID NO: 1 has unpredictable stability when formulated as an aerosol with 0.05 % (w/w) PS80.
  • Table 29 shows the results of Formulation 11 and Formulation 12, which have 0.5 % (w/w) rh-HSA as the excipient.
  • the MucilAir TM in vitro lung tissue system was used for testing of several possible forms of cytotoxicity.
  • the MucilAir TM in vitro tissue model is a functional model of human airway epithelium, is derived from cells collected from the airways of healthy donors and cultured at the air liquid interface, exhibiting a pseudostratified, ciliated epithelium which secretes mucus.
  • Manipulations of the MucilAir TM cells were performed in Class II biological containment hoods using sterile reagents and consumables.
  • Trans-epithelial electrical resistance (TEER) of the tissue was measured 3 days prior to dose application using a Millipore Millicell® ERS-2 meter with chopstick electrodes. Following TEER measurement, the apical liquid was aspirated and discarded, and the tissues tapped gently on absorbent paper to dry. Positive control response was calibrated with Sodium dodecyl sulfate, and negative control was measured with phosphate buffered saline (PBS), and a third Lysis solution was used as a lactate dehydrogenase (LDH) release benchmark.
  • TEER Trans-epithelial Electrical Resistance
  • Test samples were prepared in either pH 7.4 PBS buffer (280-330 mOsm/kg) or water and tested at multiple concentrations including 10 mg/mL, 1 mg/mL, 0.1 mg/mL, 10 ⁇ g/mL, 1 ug/mL, 100 ng/mL.
  • tissue were transferred to fresh pre-warmed media and a final media change was done immediately prior to dosing. Tissues were dosed with each concentration of test sample and controls as follows, and then returned to an incubator in standard conditions for exposure. Doses were applied to tissues by pipetting directly into the center of the apical surface.
  • the dose on the apical surface of tissues was pooled with basal media and tissue rinsed three times with pre-warmed saline (ca 0.5 mL per rinse).
  • TEER was thereafter measured again, as described for pre-dose.
  • Spent culture media (pooled with any liquid collected from the apical chamber) was retained for the LDH assay, following TEER, tested tissues underwent an ATP content assay.
  • 2 MucilAirTM tissues per treatment were exposed to 6 concentrations of each test item within a dose volume of 30 ⁇ L, for 24 hours. Doses were applied to tissues by pipetting directly into the center of the apical surface of the cells, taking care not to contact the surface with the pipette tip.
  • TEER was measured prior to dosing.
  • the release of LDH from cells was measured using the CytoTox ONETM Homogeneous Membrane Integrity Assay kit according to the manufacturer’s instructions (Promega, 2009). This assay was performed on the day of media collection. Cytotoxicity was assessed at 24 h, and compared to the benchmark LDH release controls. Duplicate aliquots (100 ⁇ L) of culture supernatant (pooled with any liquid that has permeated into the apical compartment) were collected from each well and transferred to black walled 96 well plates.
  • ATP content was assessed using the CellTiter-Glo® Luminescent Cell Viability Assay, according to the manufacturer’s instructions (Promega, 2015). Following reconstitution of the assay reagents, tissues were transferred to empty 24-well plates and assay reagent (200 ⁇ L) was added apically to each tissue. Plates were shaken for ca 10 min and then incubated for >25 min at room temperature, protected from light. Following incubation, duplicate aliquots of lysate (50 ⁇ L) from each tissue were transferred to white 96-well plates. Luminescence of wells were read using a luminometer following incubation. Blank assay reagent was also analyzed to account for background luminescence. The ATP results are shown Figure 5 and in Table 30.
  • Table 30 shows TEER values, LDH release percentage, and average ATP content for cells exposed to SEQ ID NO: 1 and SEQ ID NO: 17.
  • An initial stress response (an increase in TEER followed by a sharp decrease) was observed with both peptides at 1 –10 mg/mL.
  • Mean TEER values following experimental procedures are visualized in Figure 3.
  • a vehicle group and untreated ALI group were also measurement. Following exposure, CBF was assessed. Images of each tissue were captured at a rate of 125 frames per second (fps) at 5x or 10x magnification using a Leica DMi8 microscope with a Hamamatsu high speed digital camera. The focus was adjusted just above the cell layer to capture the cilia at their most active point. Polystyrene microbeads were diluted to ca 1:4 or more.
  • Figure 7 shows the effect of SEQ ID NO: 1, SEQ ID NO:17, and controls on the percent of active cilia within the CBF experiment.
  • Figure 8 shows the effect of treatment of test items on CBF frequency of tissue. Examples of CBF images among test samples are shown in Figure 9, Figure 10, and Figure 11.
  • Example 13 In vitro bacterial lung infection model
  • MucilAirTM tissues were inoculated with Pseudomonas aeruginosa to model lung infections and observe the effect of SEQ ID NO: 1 and SEQ ID NO: 17 on the colony forming units (CFU) measured in the cellular tissue
  • CFU colony forming units
  • Figure 15 and Figure 16 show Pseudomonas aeruginosa CFU data observed across treatment regimens following infection.
  • Figure 15 shows that treatment with higher concentration of SEQ ID NO: 1 significantly (p ⁇ 0.05) reduced the number of bacteria in apical rinse samples and that the positive control, the antibiotic Tobramycin, was very effective in reducing CFU. Given that the antibiotic control tobramycin has high cytotoxicity in vivo, this might provide a distinct advantage to treatment with SEQ ID NO: 1.
  • Figure 16 shows a one-way ANOVA of vehicle control vs both test item, confirming the ability of the 0.8 mg/mL SEQ ID NO: 1 treatment to reduce bacterial CFU.
  • Example 14 In vitro growth assay of pathogenic bacteria in the presence of SEQ ID NO: 1 and SEQ ID NO: 17
  • Bacterial growth from CF patient isolates was measured in the presence of SEQ ID NO: 1 and SEQ ID NO: 17.
  • Strains were selected from the collection of the Burkholderia cepacia Research Laboratory and Repository (BcRLR) at the University of Michigan. The strain set was enriched for isolates that were recovered from CF respiratory specimens within the last five years, are genotypically distinct, and are from diverse geographical locations in the US to avoid duplicate testing of the same strain.
  • the set was enriched for isolates previously tested for susceptibility against a custom antibiotic plate (TREK Lab Services) that included ceftazidime, ceftazidime /avibactam, ceftolozane /tazobactam, meropenem, meropenem /vaborbactam, aztreonam, colistin, minocycline, ciprofloxacin, levofloxacin, moxifloxacin, piperacillin /tazobactam, imipenem, and tigecycline.
  • MICs Minimal inhibitory concentrations
  • Peptides were serially diluted in 96 well plates (range 32 ⁇ g/ml – 250 ng/ml) in cation adjusted Mueller Hinton media (pH 7.0) or RPMI-1640 media (pH 7.0) supplemented with a final concentration of 0.165 mol/l MOPS, 0.002% Tween 80, and plates were inoculated with 10 5 CFU bacteria from overnight growth.
  • Regent controls included wells with bacteria alone (no peptide) and media alone (no bacteria or peptide).
  • Control strains included P. aeruginosa ATCC 27853, E. coli ATCC 25922, and S. aureus ATCC 29213. Strains and controls were tested in triplicate and incubated overnight at 37 o C without shaking.
  • MICs were determined using both standard visualization and spectrophotometric optical density. MICs were assigned as the lowest concentration of peptide that decreases OD by 80% relative to non-peptide controls.
  • S. aureus strains were similarly tested against clindamycin (range 4 ⁇ g/ml – 30 ng/ml), daptomycin (range 4 ⁇ g/ml – 30 ng/ml) supplemented to 50 ⁇ g/ml of calcium, linezolid (range 16 ⁇ g/ml – 120 ng/ml), trimethoprim /sulfamethoxazole [1:19] (range 16/304 ⁇ g/ml – 125/2375 ng/ml), and vancomycin (range 16 ⁇ g/ml – 120 ng/ml).

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Abstract

Provided in this disclosure are formulations and methods comprising antimicrobial peptides that can treat lung disease or injury when administered to a subject.

Description

TREATMENT OF LUNG DISEASE OR INJURY USING ENGINEERED ANTIMICROBIAL PEPTIDES CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Application No.63/245,771, filed September 17, 2021, which is incorporated by reference herein in its entirety. BACKGROUND [0002] Recurrent acute and chronic lung infections account for the majority of the morbidity and early mortality in individuals with cystic fibrosis (CF). Pseudomonas aeruginosa, methicillin- resistant S. aureus, S. maltophilia, B. cepacia, and A. xylosoxidans are bacteria that can be found in airway secretions of individuals with CF. Many of these bacteria can be resistant to antibiotics used for treating pulmonary exacerbations or infections. Antibiotic resistance is a multifactorial problem, which can include (i) physiological changes, represented by the transition from the planktonic to the biofilm mode of growth and (ii) the acquisition of antibiotic resistance adaptive mutations facilitated by frequent mutator phenotypes. New treatments that are bactericidal against multidrug resistant strains, active against biofilm, and safe and tolerable are needed to treat recurrent acute and chronic lung infections in individuals with CF. SUMMARY [0003] In some aspects, the present disclosure describes a method for treating or preventing a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg- Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg- Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val- Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val- Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg- Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg- Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 23); Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val- Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val- Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient; wherein the pharmaceutical composition comprises a pH value of at least about 4.5 to at least about 6.5. [0004] In some embodiments, the administering comprises an oral administration, an oronasal administration, an intra-nasal, an intra-tracheal, an inhalatory administration, an intravenous administration, or any combination thereof. [0005] In some aspects, the present disclosure describes a method for treating or preventing a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: (a) a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg- Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg- Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val- Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val- Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg- Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg- Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 23); Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val- Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val- Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation. [0006] Described herein are methods comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject, wherein the subject has or is at risk of having an acute or chronic lung infection caused by cystic fibrosis (CF), wherein the pharmaceutical composition comprises a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp- Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val- Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp- Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp- Arg-Arg-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg- Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg- Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 23); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg- Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg- Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg- Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation. [0007] In some embodiments, the pharmaceutical composition comprises an aerosolized composition. [0008] In some embodiments, the lung disease or injury is pneumonia. In some embodiments, the lung disease or injury is acute or chronic lung infection. In some embodiments, the acute or chronic lung infection is caused by cystic fibrosis (CF). [0009] In some embodiments, the pharmaceutical composition comprises a dry powder formulation. In some embodiments, the administering further comprises using a nebulizer, a pressurized metered-dose inhaler (MDI) a mechanical ventilator a dry powder inhaler (DPI) a soft mist inhaler, or a concentrated aerosol generator. In some embodiments, the nebulizer is a jet nebulizer, an ultrasonic nebulizer, or a vibrating mesh nebulizer. In some embodiments, the nebulizer is a vibrating mesh nebulizer. [0010] In some embodiments, the DPI is a single-dose DPI or multi-dose DPI. In some embodiments, the DPI is a reusable DPI or nonresuable DPI. In some embodiments, the pharmaceutical composition is a liquid composition. In some embodiments, the pharmaceutical composition is administered to a pulmonary system. [0011] In some embodiments, the pneumonia is hospital acquired pneumonia. In some embodiments, the hospital acquired pneumonia is ventilator acquired pneumonia. In some embodiments, the pneumonia is a bacterial pneumonia. In some embodiments, the bacterial pneumonia is caused by a bacteria selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, Staphylococcus lugdensis, methicillin-resistant Staphylococcus lugdensis, Staphylococcus haemolyticus, Staphylococcus spp., Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warnerii, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus pettenkoferi, Klebsiella pnuemoniae, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae, Enterobacter species, Cintrobacter species, Stenotrophomonas maltophilia, Acinetobacter species, Burkholderia cepacia, methicillin-resistent Staphylococcus aureus (MRSA), Haemophilus influenzae, Burkholderia multivorans, Burkholderia gladioli, Achromobacter xylosoxidans, Achromobacter dolens, Achromobacter ruhlandii, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus constellatus, Enterococcus faecalis , Enterococcus faecalis - vancomycin-susceptible, Enterococcus faecium, Enterococcus faecium - vancomycin-susceptible Corynebacterium jeikeium, Lactobacillus acidophilus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Acinetobacter baumannii, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter haemolyticus, Acinetobacter radioresistens, Enterobacter cloacae, Enterobacter aerogenes, Stenotrophomonas maltophilia, Citrobacter freundii, Citrobacter koseri, Citrobacter sedlakii, Citrobacter braakii, Morganella morganii, Providencia rettgeri, Providencia stuartii, Salmonella typhimurium, Shigella dysenteriae, Moraxella catarrhalis, Neisseria gonorrhoeae, Propionibacterium acnes, Clostridioides difficile, Clostridioides perfringens, Bacteroides fragilis, Prevotella bivia, Eggerthella lenta, Peptostreptococcus anaerobius and any combination thereof. [0012] In some embodiments, the pneumonia is a viral pneumonia. In some embodiments, the viral pneumonia is caused by a virus selected from the group consisting of influenza, respiratory syncytial cytomegalovirus and any combination thereof [0013] In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 1. In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Trp-Trp-Arg-Trp-Trp-Arg- Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17). In some embodiments, the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 17. In some embodiments, the peptide or pharmaceutically acceptable salt thereof comprises any combination of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, SEQ ID NO 10, SEQ ID NO 11, SEQ ID NO 12, SEQ ID NO 13, SEQ ID NO 14, SEQ ID NO 15, SEQ ID NO 16, and SEQ ID NO 17. [0014] In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 270 mOsm/kg to at least about 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 280 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 300 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is at least about 310 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value that is between about 280 mOsm/kg and 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises acetate. In some embodiments, the pharmaceutical composition comprises D-mannitol. In some embodiments, the pharmaceutical composition comprises D-trehalose. In some embodiments, the pharmaceutical composition comprises rh-HSA. In some embodiments, the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose. In some embodiments, the pharmaceutical composition is a dry powder. In some embodiments, the pharmaceutical composition is a liquid. In some embodiments, the pharmaceutical composition is an aerosol. In some embodiments, the pharmaceutical composition has a pH between 4.5 and 6.5. [0015] In some embodiments, the pH value is at least about 4.0 to at least about 5.5. In some embodiments the pH value is at least about 50 to at least about 55 In some embodiments the pH value is at least about 5.0. In some embodiments, the pH value is at least about 4.0 to at least about 5.5. In some embodiments, the pH value is at least about 5.5. [0016] In some embodiments, the method further comprises administering a neutrophil elastase. In some embodiments, the neutrophil elastase is human neutrophil elastase. In some embodiments, the method further comprises administering a lung surfactant. [0017] In some embodiments, the lung surfactant comprises about 25 mg/mL phospholipids, about 0.5-1.75 mg/mL triglycerides, about 1.4-3.5 mg/mL free fatty acids, and about 1.0 mg/mL protein. In some embodiments, the method further comprises inhibiting an inflammatory response. In some embodiments, the inflammatory response is quantified by measuring an expression level of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6). [0018] In some embodiments, the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.01 µg/mL to at least about 100 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.5 mg/mL to at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 0.5 mg/mL to at least about 15 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 10 mg/mL. [0019] In some embodiments, the excipient is a salt. In some embodiments, the salt is selected from the group consisting of sodium, bicarbonate, sodium chloride, sodium lactate, potassium chloride, calcium chloride, magnesium chloride, and any combination thereof. [0020] In some embodiments, the pharmaceutical composition further comprises a pH buffering agent. In some embodiments, the pH buffering agent is selected from the group consisting of (4- (2-hydroxyethyl)-1-piperazineethanesulfonic acid), sodium hydrogen phosphate, sodium phosphate, magnesium phosphate, potassium dihydrogenphosphate, sodium bicarbonate, tris(hydroxymethyl)aminomethane, sodium citrate, and any combination thereof. [0021] In some embodiments, the pharmaceutical composition further comprises a pH adjusting agent. In some embodiments, the pH adjusting agent is hydrochloric acid, sodium hydroxide, ammonium hydroxide, or any combination thereof. In some embodiments, the excipient is a sugar. [0022] In some embodiments, the pharmaceutical composition further comprises a second antibiotic. In some embodiments, the second antibiotic is selected from the group consisting of piperacillin, tazobactam, cefepime, ceftazidime, ciprofloxacin, levofloxacin, amikacin, gentamicin, tobramycin, imipenem, meropenem, linesolid, vancomycin, and any combination thereof. [0023] In some embodiments, the pharmaceutical composition further comprises a propellant. In some embodiments, the propellant is 1,1,1,2-tetrafluoroethane or 1,1,-difluoroethane. [0024] In some embodiments, the pharmaceutical composition is administered to the subject at least once per day. In some embodiments, the pharmaceutical composition is administered to the subject at least twice per day. [0025] In some embodiments, the treating or preventing lasts over a course of at least about 1 day to at least about 10 years. In some embodiments, the course is at least about 12 months. In some embodiments, the course is at least about 2 months. In some embodiments, the course is at least about 1 months. In some embodiments, the course is at least about 2 weeks. [0026] In some embodiments, the pharmaceutical composition is in form of a unit dose. [0027] In some aspects, the present disclosure describes a kit, comprising the pharmaceutical composition or the unit dose of any one of the proceeding claims and instructions for use of the pharmaceutical composition for treating or preventing pneumonia and a nebulizer. In some embodiments, the nebulizer is a vibrating mesh nebulizer. [0028] Described herein is an inhaler kit, comprising the pharmaceutical compositions described herein in an inhaler and instructions for use of the pharmaceutical composition for treating or preventing lung disease or infection. In some embodiments, the pharmaceutical composition is a dry powder. In some embodiments, the pharmaceutical composition is a liquid. In some embodiments, the pharmaceutical composition is an aerosol. In some embodiments, the pharmaceutical composition has a pH between 4.5 and 6.5. [0029] Described herein is a pharmaceutical composition for administering by inhalation comprising: a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp- Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val- Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val- Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-Trp- Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg- Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp- Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg-Val- Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val- Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 23); Arg-Val-Val- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val- Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val- Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val- Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation, and wherein the pharmaceutical composition comprises a pH value of at least about 4.5 to at least about 6.5. [0030] In some embodiments, the pharmaceutical composition is a dry powder. In some embodiments, the pharmaceutical composition is a liquid. In some embodiments, the pharmaceutical composition is an aerosol. In some embodiments, the osmolality value is between 270 mOsm/kg and 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises D-mannitol. In some embodiments, the pharmaceutical composition comprises D-trehalose. In some embodiments, the pharmaceutical composition comprises rh- HSA. In some embodiments, the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose. In some embodiments, the pharmaceutical composition further comprises a neutrophil elastase. In some embodiments, the neutrophil elastase is human neutrophil elastase. INCORPORATION BY REFERENCE [0031] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS [0032] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which: [0033] FIG.1 schematically illustrates a protocol for minimum inhibitory concentration (MIC) assay of SEQ ID NO: 1 in the presence or in the absence of surfactant. [0034] FIG.2 schematically illustrates study design for tolerability/PK (top panel) and efficacy (bottom panel). Animals will be rendered persistently neutropenic with cyclophosphamide administrations at Day -4, Day -1, Day +1 and Day +3 (circles). Animals will not be infected in tolerability/PK study (top panel) but will be intranasally (IN) infected on Day 0 in the efficacy study (bottom panel). The animals will be intratracheally (IT) and subcutaneously (SC) administered twice (BID, q12h) for 5 consecutive days. Dosing starts at 12 h post-infection for the 5 day dosing (bottom panel). The tolerability/PK study follows the same study schedule as the efficacy study with sample collection at 0.25, 2, 12, 24, 48, 72, 96 and 120 h after the last dose (top panel). For bacterial enumeration study arm groups, animals will be sacrificed at 12 h (baseline count) and 36 h post-infection post infection for determination of colony formation units (CFU). For survival study arm groups, animals will be monitored for survival up to five days (120 h). [0035] FIG.3 schematically illustrates the mean TEER (Ω*cm2) from healthy human airway epithelial cells tissues exposed to test items or control treatments. [0036] FIG.4 schematically illustrates the mean lactate dehydrogenase release from healthy human airway epithelial cells exposed to test item or control treatments. [0037] FIG.5 schematically illustrates mean ATP content (%) from healthy human airway epithelial cells exposed to test item or control treatments. [0038] FIG.6 shows mucociliary clearance from healthy human airway epithelial cells exposed to test item or control treatments. [0039] FIG.7 shows the percent of active cilia from healthy human airway epithelial cells exposed to test item or control treatments. [0040] FIG.8 shows the CBF results from healthy human airway epithelial cells exposed to test item or control treatments. [0041] FIG.9 shows an image and heat map of healthy human airway epithelial cells during control CBF experiments (Air liquid interface). [0042] FIG.10 shows an image and heat map of healthy human airway epithelial cells during CBF experiments (SEQ ID NO: 1 01 mg/mL) [0043] FIG.11 shows an image and heat map of healthy human airway epithelial cells during CBF experiments (SEQ ID NO: 17, 1 mg/mL). [0044] FIG.12 shows an image of polystyrene microbeads moving through the vehicle treated healthy human airway epithelial cells within the mucociliary clearance experiment. [0045] FIG.13 shows an image of polystyrene microbeads moving though the high dose treated healthy human airway epithelial cells within the mucociliary clearance experiment. [0046] FIG.14 schematically illustrates the mean TEER (Ω*cm2) from healthy human airway epithelial cells exposed to test items or control treatments. [0047] FIG.15 schematically illustrates the mean total CFU results analyzed from healthy human airway epithelial cells exposed to test items or control treatments. [0048] FIG.16 schematically illustrates the resulting CFU analyzed from healthy human airway epithelial cells exposed to test items or control treatments. DETAILED DESCRIPTION PHARMACEUTICAL COMPOSITION [0049] The development of antimicrobial agents is paramount due to the emergence of pathogens resistant to traditional antimicrobial compounds. Disclosed herein are peptides that comprise antimicrobial, antiviral, antifungal or antitumor activity when administered to a subject. A peptide described herein can be used to disrupt the integrity of a membrane by (a) binding to a negatively charged surface on a membrane; and/or (b) integrating into a membrane. The ability of a peptide disclosed herein to bind to a negatively charged surface on a membrane and/or integrate into a membrane can allow a peptide to act as a toxic agent to cells with a negatively charged surface by disrupting membrane integrity. In other embodiments, a peptide disclosed herein can have anti-bacterial, anti-fungal, anti-mycotic, anti-parasitic, anti-protozoal, anti-viral, anti-infectious, anti-infective and/or germicidal, algicidal, amoebicidal, microbicidal, bactericidal, fungicidal, parasiticidal, protozoacidal, and/or protozoicidal properties. [0050] The methods of treating a disease or condition described herein can be by administering to a subject a peptide or formulation containing a peptide as disclosed therein. For example, a peptide or formulation comprising a peptide described herein can be administered as an antimicrobial agent in order to at least partially inhibit the growth of a pathogen, such as bacteria, through disruption of the structural integrity of the bacterial cell membrane. A peptide described herein can be screened for broad spectrum activity against a variety of pathogens for broad utility when administered to a subject. [0051] An antimicrobial peptide described herein can also be used as a means to produce an antimicrobial film for coating a device. In some embodiments, the peptides disclosed herein can be used to coat the interior and/or exterior of a medical device, for example, an implantable medical device. The coating of a device with a peptide disclosed herein can reduce the growth and proliferation of cells, bacteria, fungi or virus on a surface coated with a peptide. In some embodiments, coating an implantable medical device with a peptide disclosed herein can reduce the risk of an infection to a subject upon implanting the medical device in a subject. [0052] It is further envisaged that a peptide described herein or formulation comprising a peptide described herein can be included in a kit. The kit can be utilized, for example, by a subject or healthcare professional to coat a device or to treat a condition or disease described herein. [0053] The antimicrobial peptides may be derived from, and are analogs of, the LLP-1 peptide parent sequence corresponding to amino acids 828- 856 of the HIV-l viral isolate HXB2R Env, (see Table 1 below). The antimicrobial activity of other LLP-1 peptide analogues has been previously described (see, Tencza et al., 1999, Journal of Antimicrobial Chemotherapy 44:33-41, U.S. Patent No.5,714,577 of Montelaro et al. and U.S. Patent No.5,945,507 of Montelaro et al., the disclosures of which are incorporated herein by reference). The antimicrobial peptides may be LLP-1 analogs having modifications based on the following principles: (i) optimizing amphipathicity, (ii) substituting arginine (Arg) on the charged face and/or valine (Val) or tryptophan (Trp) on the hydrophobic face with another amino acid, and (iii) increasing peptide length; see Table 1). Amino acid sequences are provided, left-to-right, from their N-terminus to their C-terminus in 1 letter designations and 3 letter designations. Table 1. Antimicrobial Peptides
Figure imgf000012_0001
Ile-Arg-Arg-Ile-Ile-Arg-Arg-Ile-Arg-Arg-Ile-Ile-Arg-Arg-Ile-Arg-Arg-Ile-Ile- 5 - 6 7 8 - 9 R 1 1 1 1 1 -
Figure imgf000013_0001
15 RVVRVVRRVVRR Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg 1 1 1 g 1 2 2 2 2 R 2 2
Figure imgf000014_0001
RVV Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-
Figure imgf000015_0001
[0054] In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 1. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 2. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 3. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 4. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 5. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 6. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 7. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 8. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 9. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 10. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 11. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 12. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 13. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 14. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 15. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 16. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 17. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 18. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 19. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 20. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 21. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 22. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 23 In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 24. In some embodiments, the peptide or pharmaceutically acceptable salt thereof as described herein comprises SEQ ID NO: 25. [0055] In some embodiments, the peptide or pharmaceutically acceptable salt thereof has at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 1, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 2, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 3, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 4, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 5, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 6, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 7, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 8, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 9, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 10, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 11, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 12, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 13, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 14, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 15, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 16, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 17, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 18, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 19, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 20, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 21, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 22, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 23, at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 24, or at least 70% sequence identify to a polypeptide sequence of SEQ ID NO: 25. In some embodiments, the peptide or pharmaceutically acceptable salt thereof has at least 75%, 80%, 85%, 90%, 95%, or 99% sequence identify to a polypeptide sequence listed in Table 1 and any increments of percentage therebetween. [0056] In some embodiments, the pharmaceutical formulation comprises at least one peptide described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises one or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises two or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises three or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises four or more peptides described herein as listed in Table 1 In some embodiments the pharmaceutical formulation comprises five or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises six or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises seven or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises eight or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises nine or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises ten or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises eleven or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises twelve or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises thirteen or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises fourteen or more peptides described herein as listed in Table 1. In some embodiments, the pharmaceutical formulation comprises fifteen or more peptides described herein as listed in Table 1. [0057] A peptide disclosed herein can be a salt thereof. In some embodiments, recitation of the phrases “peptide” or “polypeptide” should be construed to include a salt thereof even if not explicitly recited. In some embodiments, a salt can include a carboxylate salt (e.g. formate, acetate, trifluoroacetate, trichloroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, pamoate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or a terephthalate salts); a halide salt (e.g. chloride, bromide or iodide salts); a sulfonate salt (e.g. benzene sulfonate, methyl-, bromo- or chloro- benzenesulfonate, xylenesulfonate, methanesulfonate, trifluoromethanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2- naphthalene-sulfonate or 1,5- naphthalenedisulfonate salts); a sulfate salt; a pyrosulfate salt; a bisulfate salt; a sulfite salt; a bisulfite salt; a phosphate salt; a monohydrogenphosphate salt; a dihydrogenphosphate salt; a metaphosphate salt; a pyrophosphate salt; a nitrate salt; a chromium salt (e.g., octanoic acid); and the like. [0058] In some embodiments, amino acids of the peptides described herein can be L-amino acids. In some embodiments, amino acids of the peptides described herein can be D-amino acids. In some embodiments the peptides can have 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 D-amino acids and the rest are L-amino acids within the peptide sequence. In some embodiments, the peptides can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 L-amino acids and the rest are D- amino acids within the peptide sequence. [0059] In some embodiments, a peptide can be formulated with one or more pharmaceutically acceptable salts. In some embodiments, a pharmaceutically acceptable salt can be a salt described in Berge et al, J. Pharm. Sci, 1977. In some embodiments, a pharmaceutically acceptable salts can include those salts prepared by reaction of a peptide with a mineral, organic acid or inorganic base, such salts including, acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bitartrate, bromide, butyrate, butyn-1,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne-1,6-dioate, hydroxybenzoate, γ- hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate. metaphosphate, methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1- napthalenesulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3- phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, undeconate and xylenesulfonate. [0060] In some embodiments, a peptide can be formulated as a cleavable prodrug. The term “prodrug” as used herein, can refer to a drug precursor that, following administration to a subject and subsequent absorption, can be converted to an active, or a more active species via some process, such as conversion by a metabolic pathway. Thus, the term can encompass a derivative, which, upon administration to a recipient, can be capable of providing, either directly or indirectly, a peptide, pharmaceutically acceptable salt or a metabolite or residue thereof. Some prodrugs can have a chemical group present on a prodrug that renders it less active and/or confers solubility or some other property to the drug. Once the chemical group has been cleaved and/or modified from the prodrug the active drug can be generated. a prodrugs can be a prodrug that can increase the bioavailability of a peptide when administered to a subject (e.g., by allowing an administered peptide to be more readily absorbed) or which enhance delivery of the peptide to a biological compartment (eg the brain or lymphatic system) PH VALUE OF THE PHARMACEUTICAL COMPOSITION [0061] In some embodiments, the pharmaceutical composition described herein may comprises a pH value of about 4.5 to about 6.5. The pharmaceutical composition may comprise a pH value from 4.5 to 6.5, including increments therebetween, such as 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, or 6.5, including increments therebetween.In some embodiments, the pharmaceutical formulation described herein may further comprise a pH value of about 3.5 to about 5.5. The pharmaceutical composition may comprise a pH value from 3.5 to 5.5, including increments therebetween, such as 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, or 5.5, including increments therebetween. In some embodiments, the pharmaceutical composition has a pH of about 3.5. In some embodiments, the pharmaceutical composition has a pH of about 3.6. In some embodiments, the pharmaceutical composition has a pH of about 3.7. In some embodiments, the pharmaceutical composition has a pH of about 3.8. In some embodiments, the pharmaceutical composition has a pH of about 3.9. In some embodiments, the pharmaceutical composition has a pH of about 4.0. In some embodiments, the pharmaceutical composition has a pH of about 4.1. In some embodiments, the pharmaceutical composition has a pH of about 4.2. In some embodiments, the pharmaceutical composition has a pH of about 4.3. In some embodiments, the pharmaceutical composition has a pH of about 4.4. In some embodiments, the pharmaceutical composition has a pH of about 4.5. In some embodiments, the pharmaceutical composition has a pH of about 4.6. In some embodiments, the pharmaceutical composition has a pH of about 4.7. In some embodiments, the pharmaceutical composition has a pH of about 4.8. In some embodiments, the pharmaceutical composition has a pH of about 4.9. In some embodiments, the pharmaceutical composition has a pH of about 5.0. In some embodiments, the pharmaceutical composition has a pH of about 5.1. In some embodiments, the pharmaceutical composition has a pH of about 5.2. In some embodiments, the pharmaceutical composition has a pH of about 5.3. In some embodiments, the pharmaceutical composition has a pH of about 5.4. In some embodiments, the pharmaceutical composition has a pH of about 5.5. In some embodiments, the pharmaceutical composition may have a pH value of about a physiological value (about 7.1 to about 7.5). In some embodiments, the pharmaceutical composition may have a basic pH value of about 8.0 to 9.0. [0062] In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.6 to at least 5.5, at least 3.7 to at least 5.5, at least 3.8 to at least 5.5, at least 3.9 to at least 5.5, at least 4.0 to at least 5.5, at least 4.1 to at least 5.5, at least 4.2 to at least 5.5, at least 4.3 to at least 5.5, at least 44 to at least 55 at least 45 to at least 55 at least 46 to at least 55 at least 47 to at least 5.5, at least 4.8 to at least 5.5, at least 4.9 to at least 5.5, at least 5.0 to at least 5.5, at least 5.1 to at least 5.5, at least 5.2 to at least 5.5, at least 5.3 to at least 5.5, or at least 5.4 to at least 5.5. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.5 to at least 5.4, at least 3.5 to at least 5.3, at least 3.5 to at least 5.2, at least 3.5 to at least 5.1, at least 3.5 to at least 5.0, at least 3.5 to at least 4.9, at least 3.5 to at least 4.8, at least 3.5 to at least 4.7, at least 3.5 to at least 4.6, at least 3.5 to at least 4.5, at least 3.5 to at least 4.4, at least 3.5 to at least 4.3, at least 3.5 to at least 4.2, at least 3.5 to at least 4.1, at least 3.5 to at least 4.0, at least 3.5 to at least 3.9, at least 3.5 to at least 3.8, at least 3.5 to at least 3.7, or at least 3.5 to at least 3.6. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at least 3.5 to at least 5.5, at least 3.6 to at least 5.4, at least 3.7 to at least 5.3, at least 3.8 to at least 5.2, at least 3.9 to at least 5.1, at least 4.0 to at least 5.0, at least 4.1 to at least 4.9, at least 4.2 to at least 4.8, at least 4.3 to at least 4.7, at least 4.4 to at least 4.6, at least 4.0 to about 5.5, at least 4.5 to about 5.5, at least 5.0. [0063] In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.6 to at most 5.5, at most 3.7 to at most 5.5, at most 3.8 to at most 5.5, at most 3.9 to at most 5.5, at most 4.0 to at most 5.5, at most 4.1 to at most 5.5, at most 4.2 to at most 5.5, at most 4.3 to at most 5.5, at most 4.4 to at most 5.5, at most 4.5 to at most 5.5, at most 4.6 to at most 5.5, at most 4.7 to at most 5.5, at most 4.8 to at most 5.5, at most 4.9 to at most 5.5, at most 5.0 to at most 5.5, at most 5.1 to at most 5.5, at most 5.2 to at most 5.5, at most 5.3 to at most 5.5, or at most 5.4 to at most 5.5. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.5 to at most 5.4, at most 3.5 to at most 5.3, at most 3.5 to at most 5.2, at most 3.5 to at most 5.1, at most 3.5 to at most 5.0, at most 3.5 to at most 4.9, at most 3.5 to at most 4.8, at most 3.5 to at most 4.7, at most 3.5 to at most 4.6, at most 3.5 to at most 4.5, at most 3.5 to at most 4.4, at most 3.5 to at most 4.3, at most 3.5 to at most 4.2, at most 3.5 to at most 4.1, at most 3.5 to at most 4.0, at most 3.5 to at most 3.9, at most 3.5 to at most 3.8, at most 3.5 to at most 3.7, or at most 3.5 to at most 3.6. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt is at a pH value of at most 3.5 to at most 5.5, at most 3.6 to at most 5.4, at most 3.7 to at most 5.3, at most 3.8 to at most 5.2, at most 3.9 to at most 5.1, at most 4.0 to at most 5.0, at most 4.1 to at most 4.9, at most 4.2 to at most 4.8, at most 4.3 to at most 4.7, at most 4.4 to at most 4.6, at most 4.0 to about 5.5, at most 4.5 to about 5.5, at most 5.0. [0064] In some embodiments, the pharmaceutical composition may further comprise a pH adjusting agent such as hydrochloric acid sodium hydroxide ammonium hydroxide other pH adjusting agents known to those skilled in the art, or combinations thereof to the aqueous carrier. In some embodiments, the pH adjusting agent is hydrochloric acid. In some embodiments, the pH adjusting agent is sodium hydroxide. In some embodiments, the pH adjusting agent is ammonium hydroxide. In some embodiments, the pH adjusting agent is hydrochloric acid, sodium hydroxide, or any combination thereof. [0065] In some embodiments, the pharmaceutical composition further comprises a pH buffer or pH buffering agent. Non-limiting examples of suitable pH buffers or pH buffering agents includes sodium citrate, citric acid, sodium acetate, acetic acid, phosphoric acid, trisodium phosphate, lactic acid, sodium lactate, tartaric acid, monosodium tartrate, sodium tartrate dibasic, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), piperazine-N,N′-bis(2- ethanesulfonic acid) (PIPES), 2-(N-morpholino)ethanesulfonic acid (MES), other pH buffers known to those skilled in the art, or combinations thereof. In some embodiments, the pH buffer or pH buffering agent comprises sodium citrate. In some embodiments, the pH buffer or pH buffering agent comprises citric acid. some embodiments, the pH buffer or pH buffering agent comprises sodium acetate. In some embodiments, the pH buffer or pH buffering agent comprises acetic acid. In some embodiments, the pH buffer or pH buffering agent comprises phosphoric acid. In some embodiments, the pH buffer or pH buffering agent comprises trisodium phosphate. In some embodiments, the pH buffer or pH buffering agent comprises lactic acid. In some embodiments, the pH buffer or pH buffering agent comprises sodium lactate. In some embodiments, the pH buffer or pH buffering agent comprises tartaric acid. In some embodiments, the pH buffer or pH buffering agent comprises monosodium tartrate. In some embodiments, the pH buffer or pH buffering agent comprises sodium tartrate dibasic. In some embodiments, the pH buffer or pH buffering agent comprises 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES). In some embodiments, the pH buffer or pH buffering agent comprises piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES). In some embodiments, the pH buffer or pH buffering agent comprises 2-(N-morpholino)ethanesulfonic acid (MES). In some embodiments, the pH buffer or pH buffering agent comprises sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, potassium hydrogen phosphate, glycine, tris(hydroxymethyl)aminomethane, and any combination thereof. In some embodiments, the pH buffer or pH buffering agent comprises sodium hydrogen phosphate. In some embodiments, the pH buffer or pH buffering agent comprises sodium dihydrogen phosphate. In some embodiments, the pH buffer or pH buffering agent comprises potassium dihydrogen phosphate. In some embodiments, the pH buffer or pH buffering agent comprises potassium hydrogen phosphate. In some embodiments, the pH buffer or pH buffering agent comprises glycine In some embodiments the pH buffer or pH buffering agent comprises tris(hydroxymethyl)aminomethane. In some embodiments, the pH buffer comprises a phosphate buffer. In some embodiments, the phosphate buffer comprises Dulbecco’s phosphate buffered saline (dPBS). In some embodiments, the pH buffering agent comprises at least one of: (4-(2- hydroxyethyl)-1-piperazineethanesulfonic acid), sodium hydrogen phosphate, sodium phosphate, magnesium phosphate, potassium dihydrogenphosphate, sodium bicarbonate, tris(hydroxymethyl)aminomethane, sodium citrate, or any combination thereof. [0066] In some embodiments, the pharmaceutical formulation can be free of a pH buffering agent or pH buffer. PHARMACEUTICALLY ACCEPTABLE EXCIPIENTS [0067] At least one peptide disclosed herein can be formulated as a pharmaceutical formulation. In some embodiments, a pharmaceutical formulation can comprise a peptide described herein and at least one excipient. By “pharmaceutically acceptable”, it is meant that the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The term “compatible”, as used herein, means that the components of the formulation are capable of being commingled with the subject compound, and with each other, in a manner such that there is no interaction that would substantially reduce the pharmaceutical efficacy of the formulation under ordinary use situations. [0068] In some embodiments, a pharmaceutical formulation can comprise an excipient. An excipient can be an excipient described in the Handbook of Pharmaceutical Excipients, American Pharmaceutical Association (1986). In some embodiments, the excipient comprises acetate. In some embodiments, the excipient comprises D-mannitol. In some embodiments, the excipient comprises D-trehalose. In some embodiments, the excipient comprises human serum albumin. In some embodiments, the excipient comprises sorbitol. In some embodiments, the excipient comprises saccharin. In some embodiments, the excipient comprises sucrose. In some embodiments, the excipient comprises povidone. In some embodiments, the excipient comprises crospovidone. In some embodiments, the excipient comprises hydroxypropylcellulose. [0069] Non-limiting examples of suitable excipients can include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a chelator, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and/or a coloring agent. In some embodiments, the pharmaceutical formulation further comprises one or more additional pharmaceutically acceptable excipients. See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005) for a list of pharmaceutically acceptable excipients. In some embodiments, the pharmaceutically acceptable excipient is of sufficiently high purity and sufficiently low toxicity to render them suitable for administration preferably to an animal preferably a mammal being treated [0070] In some embodiments, an excipient can comprise a preservative. Non-limiting examples of suitable preservatives can include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol. Antioxidants can further include but not limited to EDTA, citric acid, ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), sodium sulfite, p-amino benzoic acid, glutathione, propyl gallate, cysteine, methionine, ethanol and N- acetyl cysteine. In some embodiments a preservatives can include validamycin A, TL-3, sodium ortho vanadate, sodium fluoride, N-a-tosyl-Phe- chloromethylketone, N-a-tosyl-Lys-chloromethylketone, aprotinin, phenylmethylsulfonyl fluoride, diisopropylfluorophosphate, kinase inhibitor, phosphatase inhibitor, caspase inhibitor, granzyme inhibitor, cell adhesion inhibitor, cell division inhibitor, cell cycle inhibitor, lipid signaling inhibitor, protease inhibitor, reducing agent, alkylating agent, antimicrobial agent, oxidase inhibitor, or other inhibitor. [0071] In some embodiments, an excipient can comprise a binder. Non-limiting examples of suitable binders can include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof. The binders that can be used in a pharmaceutical formulation can be selected from starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol and water or a combination thereof. [0072] In some embodiments, an excipient can comprise a lubricant. Non-limiting examples of suitable lubricants can include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil. The lubricants that can be used in a pharmaceutical formulation can be selected from metallic stearates (such as magnesium stearate, calcium stearate, aluminium stearate), fatty acid esters (such as sodium stearyl fumarate), fatty acids (such as stearic acid), fatty alcohols, glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oils, leucine, polyethylene glycols (PEG), metallic lauryl sulphates (such as sodium lauryl sulphate, magnesium lauryl sulphate), sodium chloride, sodium benzoate, sodium acetate and talc or a combination thereof. [0073] In some embodiments, an excipient can comprise a dispersion enhancer. Non-limiting examples of suitable dispersants can include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants. [0074] In some embodiments, an excipient can comprise a disintegrant. In some embodiments a disintegrant can be a non-effervescent disintegrant. Non-limiting examples of suitable non- effervescent disintegrants can include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth. In some embodiments a disintegrant can be an effervescent disintegrant. Non- limiting examples of suitable effervescent disintegrants can include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid. [0075] In some embodiments, an excipient can comprise a flavoring agent. Flavoring agents incorporated into an outer layer can be chosen from synthetic flavor oils and flavoring aromatics; natural oils; extracts from plants, leaves, flowers, and fruits; and combinations thereof. In some embodiments a flavoring agent can be selected from the group consisting of cinnamon oils; oil of wintergreen; peppermint oils; clover oil; hay oil; anise oil; eucalyptus; vanilla; citrus oil such as lemon oil, orange oil, grape and grapefruit oil; and fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple, and apricot. [0076] In some embodiments, an excipient can comprise a sweetener. Non-limiting examples of suitable sweeteners can include glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as a sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; and sugar alcohols such as sorbitol, mannitol, sylitol, and the like. In some embodiments, the excipient may be a sugar. Non-limiting examples of suitable sugars can include glucose, sucrose, dextrose, lactose, maltodextrin, fructose, and mixtures thereof. [0077] In some embodiments, an excipient can comprise a coloring agent. Non-limiting examples of suitable color agents can include food, drug and cosmetic colors (FD&C), drug and cosmetic colors (D&C), and external drug and cosmetic colors (Ext. D&C). A coloring agent can be used as dyes. [0078] In some embodiments, an excipient can comprise an isotonicity agent. Examples can include, but are not limited to: sodium chloride, calcium chloride, potassium chloride, sodium lactate, copper chloride, copper sulfate, monopotassium phosphate, sucrose, dextrose, or glucose. In some embodiments the isotonicity agent is sodium chloride [0079] In some embodiments, an excipient can comprise a chelator. In some embodiments, a chelator can be a fungicidal chelator. Examples can include, but are not limited to: ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA); a disodium, trisodium, tetrasodium, dipotassium, tripotassium, dilithium and diammonium salt of EDTA; a barium, calcium, cobalt, copper, dysprosium, europium, iron, indium, lanthanum, magnesium, manganese, nickel, samarium, strontium, or zinc chelate of EDTA; trans-1,2-diaminocyclohexane-N,N,N',N'- tetraaceticacid monohydrate; N,N-bis(2-hydroxyethyl)glycine; 1,3-diamino-2-hydroxypropane- N,N,N',N'-tetraacetic acid; 1,3-diaminopropane-N,N,N',N'-tetraacetic acid; ethylenediamine- N,N'-diacetic acid; ethylenediamine-N,N'-dipropionic acid dihydrochloride; ethylenediamine- N,N'-bis(methylenephosphonic acid) hemihydrate; N-(2-hydroxyethyl)ethylenediamine-N,N',N'- triacetic acid; ethylenediamine-N,N,N',N'-tetrakis(methylenephosponic acid); O,O'-bis(2- aminoethyl)ethyleneglycol-N,N,N',N'-tetraacetic acid; N,N-bis(2- hydroxybenzyl)ethylenediamine-N,N-diacetic acid; 1,6-hexamethylenediamine-N,N,N',N'- tetraacetic acid; N-(2-hydroxyethyl)iminodiacetic acid; iminodiacetic acid; 1,2-diaminopropane- N,N,N',N'-tetraacetic acid; nitrilotriacetic acid; nitrilotripropionic acid; the trisodium salt of nitrilotris(methylenephosphoric acid); 7,19,30-trioxa-1,4,10,13,16,22,27,33- octaazabicyclo[11,11,11] pentatriacontane hexahydrobromide; or triethylenetetramine- N,N,N',N",N'",N'"-hexaacetic acid. [0080] In some embodiments, an excipient can comprise a diluent. Non-limiting examples of diluents can include water, glycerol, methanol, ethanol, and other similar biocompatible diluents. In some embodiments, a diluent can be an aqueous acid such as acetic acid, citric acid, maleic acid, hydrochloric acid, phosphoric acid, nitric acid, sulfuric acid, or similar. In other cases, a diluent can be selected from a group comprising alkaline metal carbonates such as calcium carbonate; alkaline metal phosphates such as calcium phosphate; alkaline metal sulphates such as calcium sulphate; cellulose derivatives such as cellulose, microcrystalline cellulose, cellulose acetate; magnesium oxide, dextrin, fructose, dextrose, glyceryl palmitostearate, lactitol, caoline, lactose, maltose, D-mannitol, simethicone, sorbitol, starch, pregelatinized starch, talc, xylitol and/or anhydrates, hydrates and/or pharmaceutically acceptable derivatives thereof or combinations thereof. [0081] In other embodiments, an excipient can comprise a surfactant. Surfactants can be selected from, but not limited to, polyoxyethylene sorbitan fatty acid esters (polysorbates), sodium lauryl sulphate, sodium stearyl fumarate, polyoxyethylene alkyl ethers, sorbitan fatty acid esters, polyethylene glycols (PEG), polyoxyethylene castor oil derivatives, docusate sodium, quaternary ammonium compounds, amino acids such as L- leucine, sugar esters of fatty acids, glycerides of fatty acids or a combination thereof [0082] In some embodiments, an excipient can comprise an aqueous carrier. In some embodiments, the aqueous carrier is lactated Ringer’s solution, normal saline (0.9% w/v), or aqueous sodium carbonate. In some embodiments, the aqueous carrier is lactated Ringer’s solution. In some embodiments, the aqueous carrier is normal saline (0.9% w/v). In some embodiments, the aqueous carrier is aqueous sodium bicarbonate. In some embodiments, the aqueous carrier is physiologically isotonic, physiologically hypotonic, or physiologically hypertonic. In some embodiments, the aqueous carrier is physiologically isotonic. In some embodiments, the aqueous carrier is physiologically hypotonic. In some embodiments, the aqueous carrier is physiologically hypotonic (sub-physiologic osmolarity or osmolality), for example, modified versions of lactated Ringer’s solution, normal saline (0.9% w/v), or aqueous sodium bicarbonate diluted with water. In some embodiments, the aqueous carrier is physiologically hypertonic. In some embodiments, the aqueous carrier has a total osmolarity ranging from about 1 milliosmole per one liter (mOsm/L) to about 5,000 mOsm/L. In some embodiments, the aqueous carrier has a total osmolarity of about 1 mOsm/L, about 50 mOsm/L, about 100 mOsm/L, about 150 mOsm/L, about 200 mOsm/L, about 250 mOsm/L, about 300 mOsm/L, about 350 mOsm/L, about 400 mOsm/L, about 450 mOsm/L, about 500 mOsm/L, about 1000 mOsm/L, about 1500 mOsm/L, about 2000 mOsm/L, about 2500 mOsm/L, about 3000 mOsm/L, about 3500 mOsm/L, about 4000 mOsm/L, about 4500 mOsm/L, or about 5000 mOsm/L. In some embodiment, the aqueous carrier has a total osmolality ranging from about 1 milliosmole per kilogram (mOsm/kg) from 5000 mOsm/kg. In some embodiments, the aqueous carrier has a total osmolarity of about 1 mOsm/kg, about 50 mOsm/kg, about 100 mOsm/kg, about 150 mOsm/kg, about 200 mOsm/kg, about 250 mOsm/kg, about 300 mOsm/kg, about 350 mOsm/kg, about 400 mOsm/kg, about 450 mOsm/kg, about 500 mOsm/kg, about 1000 mOsm/kg, about 1500 mOsm/kg, about 2000 mOsm/kg, about 2500 mOsm/kg, about 3000 mOsm/kg, about 3500 mOsm/kg, about 4000 mOsm/kg, about 4500 mOsm/kg, or about 5000 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of about 270 mOsm/kg to about 350 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 270 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 280 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 290 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 300 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 310 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 320 mOsm/kg In some embodiments the pharmaceutical composition comprises an osmolality value of at least about 330 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 340 mOsm/kg. In some embodiments, the pharmaceutical composition comprises an osmolality value of at least about 350 mOsm/kg. In some embodiments, the aqueous carrier may have a total ionic strength ranging from about 0.001 molar (M) and 1.0 M. In some embodiments, aqueous carrier may have a total ionic strength of about 0.001 M, about 0.01 M, about 0.015 M, about 0.02 M, about 0.025 M, about 0.03 M, about 0.035 M, about 0.04 M, about 0.05 M, about 0.055 M, about 0.06 M, about 0.065 M, about 0.07 M, about 0.075 M, about 0.08 M, about 0.085 M, about 0.09 M, about 0.1 M, about 0.12 M, about 0.14 M, about 0.15 M, about 0.16 M, about 0.18 M, about 0.2 M, about 0.22 M, about 0.24 M, about 0.25 M, about 0.26 M, about 0.28 M, about 0.03 M, about 0.35 M, about 0.4 M, about 0.45 M, about 0.5 M, about 0.55 M, about 0.6 M, about 0.65 M, about 0.7 M, about 0.75 M about 0.8 M, about 0.85 M, about 0.9 M, about 0.95 M, or about 1.0 M. [0083] In some embodiments, the pharmaceutical formulation is in the form of a tablet, a liquid, a syrup, an oral formulation, an intravenous formulation, an intranasal formulation, an ocular formulation, an otic formulation, a subcutaneous formulation, an inhalation formulation, a suppository, and any combination thereof. A weight fraction of an excipient or combination of excipients in a pharmaceutical formulation can be less than about 80%, 70%, 60%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, or 1% as compared to a total weight of a pharmaceutical formulation. See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005). METHODS OF TREATMENT [0084] Provided herein are methods of treating or preventing lung disease or injury comprising administering a pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt thereof as described herein. [0085] In some embodiments, the lung disease or injury is pneumonia. In some embodiments, the pneumonia is a viral pneumonia. In some embodiments, the viral pneumonia is caused by a virus selected from influenza, respiratory syncytial, cytomegalovirus, and any combination thereof. In some embodiments, the the pneumonia is a bacterial pneumonia. In some embodiments, the bacterial pneumonia is caused by a bacteria selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, Staphylococcus lugdensis, methicillin-resistant Staphylococcus lugdensis, Staphylococcus haemolyticus, Staphylococcus spp., Staphylococcus hominis, Staphylococcus saprophyticus Staphylococcus simulans Staphylococcus warnerii Staphylococcus capitis Staphylococcus caprae, Staphylococcus pettenkoferi, Klebsiella pnuemoniae, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae, Enterobacter species, Cintrobacter species, Stenotrophomonas maltophilia, Acinetobacter species, Burkholderia cepacia, methicillin-resistent Staphylococcus aureus (MRSA), Haemophilus influenzae, Burkholderia multivorans, Burkholderia gladioli, Achromobacter xylosoxidans, Achromobacter dolens, Achromobacter ruhlandii, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus constellatus, Enterococcus faecalis , Enterococcus faecalis - vancomycin-susceptible, Enterococcus faecium, Enterococcus faecium - vancomycin-susceptible Corynebacterium jeikeium, Lactobacillus acidophilus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Acinetobacter baumannii, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter haemolyticus, Acinetobacter radioresistens, Enterobacter cloacae, Enterobacter aerogenes, Stenotrophomonas maltophilia, Citrobacter freundii, Citrobacter koseri, Citrobacter sedlakii, Citrobacter braakii, Morganella morganii, Providencia rettgeri, Providencia stuartii, Salmonella typhimurium, Shigella dysenteriae, Moraxella catarrhalis, Neisseria gonorrhoeae, Propionibacterium acnes, Clostridioides difficile, Clostridioides perfringens, Bacteroides fragilis, Prevotella bivia, Eggerthella lenta, Peptostreptococcus anaerobius, or any other bacteria known to those skilled in the art to be capable of infecting a patient or subject and combinations thereof. In some embodiments, the bacteria can be antibiotic-tolerant or antibiotics-resistant. [0086] In some embodiments, the pneumonia can arise from the subject being exposed to bacteria in a hospital setting. In some embodiments, the pneumonia can arise from a ventilator. Often, when patients are suffering from pneumonia, biofilms may be formed on a living (e.g., lung) or non-living surface (e.g., catheters, endotracheal tubes, etc.). In some embodiments, the pneumonia is hospital acquired pneumonia. In some embodiments, the pneumonia is ventilator acquired pneumonia. [0087] In some embodiments, the lung disease or injury is an acute lung infection or a chronic lung infection. In some embodiments, the lung disease or injury is caused by cystic fibrosis. In some embodiments, the lung disease or injury is complicated by cystic fibrosis. [0088] In some embodiments, administering the pharmaceutical composition described herein may comprise an oral administration, an oronasal administration, an intra-nasal, an intra-trachael, an inhalatory administration, an intravenous administration, any other administrative routes known to those skilled in the art, or any combination thereof. In some embodiments, administration of the peptide or pharmaceutically acceptable salt may be administered in formulations containing conventionally acceptable carriers, adjuvants, and vehicles as desired. In some embodiments administration of the pharmaceutical composition further comprises administration of neutrophil elastase. In some embodiments, the neutrophil elastase is human neutrophil elastase. [0089] In some embodiments, the administration may be through injection or infusion, including intra-arterial, intracardiac, intraperitoneal, intrathecal, intravascular, intravenous, subcutaneous, inhalational, transdermal, transmucosal, sublingual, buccal, dermal, intranasal, any other method of administration known to those skilled in the art, or any combinations thereof. [0090] In some embodiments, the method may comprise draining liquid in the lungs (thoracentesis) prior to administering the pharmaceutical composition described herein. In some embodiments, the method can further comprise administering an additional antibiotic or an antiviral compound. In some embodiments, an antibiotic course can be administered before, during, or after administering the pharmaceutical composition described herein. [0091] In some embodiments, the method of administration may last over a course of at least about 1 hour, 5 hours, 12 hours, 24 hours, 48 hours, 72 hours, 4 days, 5 days, 1 week, 2 weeks, 3 week, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 20 years, 25 years, 30 years, 35 years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years, 70 years, 75 years, or 80 years. [0092] Administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt thereof may be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times a day. In some embodiments, pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be delivered more than once a day. In some embodiments, peptide or pharmaceutically acceptable salt present may be delivered more than twice a day. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 1 day to at least about 12 months. In some embodiments, the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 2 months. In some embodiments, pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 1 months. In some embodiments, pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may be administered over a course of at least about 2 weeks. [0093] In some embodiments, administration of a pharmaceutical composition comprising a peptide may be performed at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 times a week. In some embodiments, administration of a peptide, salt, or pharmaceutical composition comprising a peptide may be performed at least 1 2 3 4 5 6 7 8 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90 times a month. [0094] In some embodiments, the method disclosed herein can lead to at least about 10% reduction in bacterial burden, at least about 20% reduction in bacterial burden, at least about 30% reduction in bacterial burden, at least about 40% reduction in bacterial burden, at least about 50% reduction in bacterial burden, at least about 60% reduction in bacterial burden, at least about 70% reduction in bacterial burden, at least about 80% reduction in bacterial burden, at least about 90% reduction in bacterial burden, at least about 90% reduction in bacterial burden, at least about 91% reduction in bacterial burden, at least about 92% reduction in bacterial burden, at least about 93% reduction in bacterial burden, at least about 94% reduction in bacterial burden, at least about 95% reduction in bacterial burden, at least about 96% reduction in bacterial burden, at least about 97% reduction in bacterial burden, at least about 98% reduction in bacterial burden, at least about 99% reduction in bacterial burden, at least about 99.9% reduction in bacterial burden, at least about 99.99% reduction in bacterial burden, or any increments therebetween. [0095] In some embodiments, administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may occur over a time period of from at least about 0.5 min to at least about 30 min. In some embodiments, delivery of pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt may occur over a time period of at least about 15 min. [0096] In some embodiments, administration of the pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt occurs over a time period of from at least about 0.5 min to at least about 1 min, from at least about 1 min to at least about 2 min, from at least about 2 min to at least about 3 min, from at least about 3 min to at least about 4 min, from at least about 4 min to at least about 5 min, from at least about 5 min to at least about 6 min, from at least about 6 min to at least about 7 min, from at least about 7 min to at least about 8 min, from at least about 8 min to at least about 9 min, from at least about 9 min to at least about 10 min, from at least about 10 min to at least about 11 min, from at least about 11 min to at least about 12 min, from at least about 12 min to at least about 13 min, from at least about 13 min to at least about 14 min, from at least about 14 min to at least about 15 min, from at least about 15 min to at least about 16 min, from at least about 16 min to at least about 17 min, from at least about 17 min to at least about 18 min, from at least about 18 min to at least about 19 min, from at least about 19 min to at least about 20 min from at least about 21 min to at least about 22 min from at least about 22 min to at least about 23 min, from at least about 23 min to at least about 24 min, from at least about 24 min to at least about 25 min, from at least about 25 min to at least about 26 min, from at least about 26 min to at least about 27 min, from at least about 27 min to at least about 28 min, from at least about 28 min to at least about 29 min, or from at least about 29 min to at least about 30 min. INHIBITING INFLAMMATORY RESPONSE [0097] In some embodiments, the pharmaceutical formulation described herein may have an anti-inflammatory effect on a subject. In some embodiments, the anti-inflammatory effect may be inhibiting a cytokine response in the subject during the treatment for pneumonia or other chronic lung disease, such as cystic fibrosis. In some embodiments, the anti-inflammatory effect may be reducing the levels of a cytokine due to an infection. In some embodiments, the anti- inflammatory effect may be reducing the rise in the levels of a cytokine due to said infection. In some embodiments, the cytokine may comprise at least one of: interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin- 9, interleukin-10, interleukin-11, interleukin-12, interleukin-13, interleukin-14, interleukin-15, interleukin-16, interleukin-17, interleukin-18, interleukin-19, interleukin-20, interleukin-21, interleukin-22, interleukin-23, interleukin-24, interleukin-25, interleukin-26, interleukin-27, interleukin-28, interleukin-29, interleukin-30, interleukin-31, interleukin-32, interleukin-33, interleukin-34, interleukin-35, interleukin-36, a chemokine, an interferon, a lymphokine, or tumor necrosis factor-α (TNF-α). [0098] In some embodiments, the anti-inflammatory effect may be reducing tissue destruction caused by inflammation. In some embodiments, the anti-inflammatory effect may be reducing tissue destruction caused by an infection. INHALATION FORMULATION AND ADMINISTRATION [0099] In certain embodiments, the described pharmaceutical composition here is in the form of an inhalation formulation. In some embodiments, the described pharmaceutical composition comprises a dry powder formulation. In other embodiments, the described pharmaceutical composition comprises a liquid formulation. In some embodiments, inhalation of the pharmaceutical composition described herein may be facilitated by an aerosolization device or inhaler. In some embodiments, the aerosolization device or inhaler is a nebulizer, a pressurized metered-dose inhaler (MDI), a mechanical ventilator, a soft mist inhaler, a concentrated aerosol generator, or a dry powder inhaler (DPI). Efficient drug delivery to the lungs through nebulizers is dependent on several factors including inhaler device, formulation, and inhalation maneuver. In some embodiments the aerosolization device or inhaler is dependent on the pharmaceutical composition in the form of a liquid. In some embodiments, the aerosolization device or inhaler is dependent on the pharmaceutical composition in the form of a solid or an inhalable dry powder. [0100] In some embodiments, a nebulizer is selected on the basis of allowing the formation of an aerosol of the pharmaceutical composition described herein. Nebulizers can impart energy into a liquid pharmaceutical composition to aerosolize the liquid, and to allow delivery to the pulmonary system, e.g., the lungs, of a patient. A nebulizer comprises a liquid delivery system, such as a container having a reservoir that contains a liquid pharmaceutical composition. The aerosolization device can comprise the extrusion of the pharmaceutical preparation through micron or submicron-sized holes with subsequent Rayleigh break-up into fine droplets. As such, an inhaler can comprise a canister containing the droplets or droplets and propellant, and wherein the inhaler comprises a metering valve in communication with an interior of the canister. The propellant can be a hydrofluoroalkane. For instance, the pharmaceutical composition can be in liquid solution, and can be administered with nebulizers, in order to provide an aerosolized medicament that can be administered to the pulmonary air passages of a patient in need thereof. Nebulizers known in the art can easily be employed for administration of the claimed formulations. Breath-activated or breath-actuated nebulizers, as well as those comprising other types of improvements which have been, or will be, developed are also compatible with the formulations of the present disclosure and are contemplated as being within the scope thereof. [0101] In some embodiments, the propellant is a fluorocarbon. In some embodiments, the fluorocarbon is a perfluorocarbon. In some embodiments, the fluorocarbon is a partially fluorinated carbon. In some embodiments, the propellant is a pharmaceutically acceptable fluorocarbon. In some embodiments, the propellant is 1,1,1,2-tetrafluoroethane (HFA 134a). In some embodiments, the propellant is 1,1-difluoroethane (HFA 152a). [0102] In some embodiments, the nebulizer is an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber. In some embodiments, the nebulizer is jet nebulizer, an ultrasonic nebulizer, or a vibrating mesh nebulizer. In some embodiments, the nebulizer is a breath activated or breath-actuated nebulizer. In some embodiments, the nebulizer is a hand-held inhaler device (e.g., a Breath Actuated Nebulizer (BAN)). In some embodiments, the nebulizer has a compressed air source. In some embodiments, the nebulizer converts the liquid pharmaceutical composition into an aerosol. In some embodiments, the nebulizer converts liquid medication into an aerosol by extruding the pharmaceutical preparation through micron or submicron-sized holes. In some embodiments, the nebulizer converts liquid medication into an aerosol so it can be inhaled into the lungs. In some embodiments, the nebulizer is a small volume nebulizer. In some embodiments, aerosolized medication is only produced when inhaled through the device. [0103] In some embodiments, a jet nebulizer that utilizes compressed gas is forced through an orifice in the container may be used to administer the liquid pharmaceutical composition. The compressed gas forces liquid to be withdrawn through a nozzle, and the withdrawn liquid can mix with the flowing gas to form aerosol droplets. A cloud of droplets can then be administered to the patient’s respiratory tract. In some embodiments, the nebulizer is a small volume jet nebulizer. [0104] In some embodiments, the nebulizer is a vibrating mesh nebulizer. In some embodiments, the vibrating mesh nebulizer uses mechanical energy to vibrates a mesh. This vibration of the mesh aerosolizes the liquid pharmaceutical composition to create an aerosol cloud that is administered to the patient’s lungs. Other examples of nebulizers include, but are not limited to, the Aeroneb®Go or Aeroneb®Pro nebulizers, available from Aerogen Ltd. of Galway, Ireland; the PARI eFlow and other PARI nebulizers available from PARI Respiratory Equipment, Inc. of Midlothian, Va.; the Lumiscope® Nebulizer 6600 or 6610 available from Lumiscope Company, Inc. of East Brunswick, N.J.; and the Omron NE-U22 available from Omron Healthcare, Inc. of Kyoto, Japan. Other examples of nebulizers include devices produced by Medspray (Enschede, The Netherlands). In some embodiments, the vibrating mesh nebulizer can be used without compressed gas. By generating fine droplets by using a vibrating perforated or unperforated membrane, rather than by introducing compressed air, the aerosolized pharmaceutical composition can be introduced without substantially affecting the flow characteristics. In addition, the generated droplets when using a nebulizer of this type are introduced at a low velocity, thereby decreasing the likelihood of the droplets being driven to an undesired region. [0105] The pharmaceutical compositions disclosed herein can also be administered to the lungs of a patient via aerosolization, such as with a metered dose inhaler (MDI). Metered dose inhalers known in the art can be employed for administration of the claimed pharmaceutical compositions. Breath-activated or breath-actuated MDIs and pressurized MDIs (pMDIs), as well as those comprising other types of improvements which have been, or will be, developed are also compatible with the formulations of the present disclosure and, as such, are contemplated as being within the scope thereof. Propellant-based systems may use suitable pressurized metered- dose inhalers (pMDIs). [0106] Dry powders can use dry powder inhaler devices (DPIs), which are capable of dispersing the drug substance effectively. Dry powder inhaler devices can use a variety of dosage containers (e.g., capsule, blister pack, blister strip, reservoir, cartridge). Efficient drug delivery to the lungs through dry powder inhalers (DPIs) is dependent on several factors including inhaler device formulation, and inhalation maneuver. In some embodiments, dry powder formulations of the pharmaceutical compositions described herein may be formulated for characteristics at particulate and bulk level to ensure the drug delivery to lower airway regions. In some embodiments, the DPI are pre-filled with doses of the pharmaceutical composition. In some embodiments, the DPI are pre-filled with a single dose. In some embodiments, the DPI are pre- filled with multiple doses. In some embodiments, the DPI is disposable after usage. In some embodiments, the DPI or aerosolized device does not contain a capsule for the pharmaceutical composition, while the device itself has a compartment or compartments for filling and/or refilling of the pharmaceutical composition. In some embodiments, the DPI uses a capsule comprising the pharmaceutical composition. In some embodiments, the DPI or aerosolization device requires inhalation of the patient to aerosolize the pharmaceutical composition. In some embodiments, the DPI is a single-dose DPI or a multi-dose DPI. In some embodiments, the DPI is a reusable DPI or a non-reusable DPI. [0107] In some embodiments, dry powder formulations can blend micronized drug particles (less than 5 micron in size) with larger carrier particles to address flowability and dose variability issues. In some embodiments, the concentration of drug in drug-carrier dry powder formulations is low (e.g., 1 drug.: 67.5 carrier). In some embodiments, the concentration of drug in drug- carrier dry powder formulations vary depending on the aerosol dispersion properties of the formulation. Therefore, during drug-carrier mixing, drug particles will preferably adhere to the active binding sites (more adhesive areas) on the carrier surface and expected to separate from carrier surface upon inhalation. Drug re-dispersion is considered most important for getting drug particles into deep lung airway regions. Usually, only small amounts of drug reach the lower airway regions due to strong drug-carrier adhesion. Indeed, drug re-dispersion is a function of balance between cohesive forces (between the drug particles) and the adhesive forces (between drug and carrier particles). In order to aerosolize drug particles, patient inspiratory force should overcome drug-carrier adhesive forces which are dependent on physicochemical properties of both drug particles and carrier particles. Consequently, it can be desirable to control the characteristics of carrier particles in terms of size, morphology, crystal form, surface energy. It has been reported that the differences in carrier particle size is likely to have significant impact on DPI aerosolization performance. The presence of fine particles on carrier surface can decrease the drug-carrier contact area and consequently drug-carrier adhesion forces leading to improved DPI performance. Better aerosolization performance was observed when the carrier tap density was higher, whereas no correlation was found between carrier flowability and DPI performance. Carriers with reduced dispersive surface energy produced higher fine particle fraction (FPF) of the drug upon aerosolization. Carrier particles with higher elongation ratio or increased surface roughness showed favorable inhalation properties. [0108] In some cases, a nebulizer may be used to deliver the pharmaceutical composition in an acute care setting for a short period (7 or less days). In some cases, a nebulizer may be used to deliver the pharmaceutical composition as an adjunct therapy to standard of care antibiotics. In some cases, a nebulizer may be used to deliver the pharmaceutical composition to rapidly reduce bacterial burden in the lung in recurrent acute and chronic lung infections in individuals with cystic fibrosis. DROPLET / PARTICLE SIZE [0109] The distribution of aerosol droplet of a liquid pharmaceutical composition described herein or a particle of a dry powder pharmaceutical composition as described herein of an inhalable can be expressed in terms of either: the mass median aerodynamic diameter (MMAD) — the size at which half of the mass of the aerosol is contained in smaller droplets and half in larger droplets; volumetric mean diameter (VMD); mass median diameter (MMD); the fine droplet fraction (FDF) or the fine particle fraction (FPF) - the percentage of droplets/particle that are <5 um in diameter. These measures have been used for comparisons of the in vitro performance of different nebulizers and drug combinations. [0110] In some embodiments, the higher the fine droplet fraction or fine particle fraction, the higher the proportion of the emitted dose that is to deposit the lung. Inhaled droplets/particles are subject to deposition by one of two mechanisms: impaction, which usually predominates for larger droplets/particles, and sedimentation, which is prevalent for smaller droplets/particles. Impaction occurs when the momentum of an inhaled droplet/particle is large enough that the droplet/particle does not follow the air stream and encounters a physiological surface. In contrast, sedimentation occurs primarily in the deep lung when very small droplets/particles which have traveled with the inhaled air stream encounter physiological surfaces as a result of random diffusion within the air stream. [0111] For pulmonary administration, the upper airways are avoided in favor of the middle and lower airways. Pulmonary drug delivery can be accomplished by inhalation of an aerosol through the mouth and throat. Droplets having a mass median aerodynamic diameter (MMAD) of greater than about 5 microns generally do not reach the lung; instead, they tend to impact the back of the throat and are swallowed and possibly orally absorbed. Droplets/particles having diameters of about 1 to about 5 microns are small enough to reach the upper-to-mid-pulmonary region (conducting airways) but may be too large to reach the alveoli. Smaller droplets/particles, ie about 05 to about 2 microns are capable of reaching the alveolar region Droplets/particles having diameters smaller than about 0.5 microns can also be deposited in the alveolar region by sedimentation, although very small droplets/particles can be exhaled. Measures of droplet/particle size can be referred to as volumetric mean diameter (VMD), mass median diameter (MMD), or MMAD. These measurements can be made by impaction (MMD and MMAD) or by laser (VMD). For liquid particles, VMD, MMD and MMAD may be the same if environmental conditions are maintained, e.g., standard humidity. However, if humidity is not maintained, MMD and MMAD determinations will be smaller than VMD due to dehydration during impactor measurements. For the purposes of this description, VMD, MMD and MMAD measurements are considered to be under standard conditions such that descriptions of VMD, MMD and MMAD will be comparable. [0112] In some embodiments, droplet/particle size or aerosolized pharmaceutical composition described herein has a MMAD of about 1 µm to about 5 µm. In some embodiments, droplet/particle size or aerosolized pharmaceutical composition described herein has a MMAD of about 1 µm, 1.5 µm, 2.0 µm, 2.5 µm, 3.0 µm, 3.5 µm, 4.0 µm, 4.5 µm, or about 5 µm. In some embodiments, the nebulizer generates an average droplet size of about 1 µm, 1.5 µm, 2.0 µm, 2.5 µm, 3.0 µm, 3.5 µm, 4.0 µm, 4.5 µm, or about 5 µm MMAD. In some embodiments, the DPI generates an average particle size of about 1 µm, 1.5 µm, 2.0 µm, 2.5 µm, 3.0 µm, 3.5 µm, 4.0 µm, 4.5 µm, or about 5 µm MMAD. [0113] For dry powders, the moisture content is typically less than about 15 wt %, such as less than about 10 wt %, less than about 5 wt %, less than about 2 wt %, less than about 1 wt %, or less than about 0.5 wt %. [0114] In some embodiments, the nebulizer / DPI generates an average flow rate of 0.4 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.5 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.6 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.7 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.8 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 0.9 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 1.0 mL/min. In some embodiments, the nebulizer generates an average flow rate of 1.1 mL/min. In some embodiments, the nebulizer / DPI generates an average flow rate of 1.2 mL/min. Biofilm [0115] A microbial film can refer to a consortium comprising microorganisms and extracellular material. In some cases, microorganisms may comprise one or more pathogenic bacteria that can harm a host organism In some cases the one or more pathogenic bacteria may excrete various chemicals including polysaccharides and proteins, which can form an extracellular matrix. In some cases, the extracellular matrix can provide a stabilizing and protective layer for the one or more pathogenic bacteria, such that the one or more pathogenic bacteria within the extracellular matrix exhibit a much higher resistance to antibiotics than the one or more pathogenic bacteria would exhibit in the absence of the extracellular matrix. In some cases, a biofilm may reduce the overall metabolic rate of bacteria, which may contribute to the increased resistance of pathogenic bacteria to the one or more antibiotics. [0116] In some cases, a microbial film can develop on various surfaces of a host organism. Depending on the locus of an initial infection with one or more pathogenic bacteria, a microbial film may develop over time as the pathogenic bacteria grow in number and excrete the various chemicals. In some cases, an infection may spread from the locus of the initial infection to other areas of the host organism. [0117] In some cases, a microbial film may develop on a surface of in the respiratory tract of a human being. In some cases, the surface may be within a nasal cavity, an oral cavity, a pharynx, a larynx, a trachea, a bronchus, a bronchi, a alveoli, or a lung. In some cases, the surface may form a structure or a substructure of any of the aforementioned organs and tissues. [0118] In some cases, a microbial film may develop on various surfaces of a medical device. For example, a patient in intensive care may sometimes be given tracheal intubation to assist the patient’s breathing. Bacteria on an intubation device may enter the respiratory of the tract, and lead to an infection. In another example, a patient may be provided a ventilator in certain hospital settings or in certain medical procedure. Bacteria on the ventilator may enter the respiratory tract and lead to an infection. In some cases, the infection may lead to pneumonia. [0119] Various medical devices may lead to an infection of the respiratory of a human being. In some cases, the medical device may be used to assist in breathing. In some cases, the medical device may be used for diagnostics. In some cases, the medical device may be a suction device. In some cases, the medical device may be a tube that is configured to be inserted into at least a portion of the human being’s respiratory system. In some cases, the medical device may be an inhaler. In some cases, the medical device may be a bronchoscopy endoscope, a tracheostomy tube, a spirometer, a positive airway pressure system, or a laryngectomy tube. [0120] In some cases, it may be desirable to prevent a respiratory infection in a human being with a prophylactic treatment of the human being’s respiratory tract. In some cases, a patient may be prophylactically treated with a method of the present disclosure to prevent an infection. In some cases, a patient may be prophylactically treated with a pharmaceutical composition of the present disclosure to prevent an infection. In some cases, a patient may be prophylactically treated with a system of the present disclosure to prevent an infection [0121] In some cases, it may be desirable to treat a respiratory infection in a human being s respiratory tract before a biofilm has developed. In events where an infection has occurred within the respiratory tract of a patient, the infection may be treated with a method of the present disclosure. In events where an infection has occurred within the respiratory tract of a patient, the infection may be treated with a pharmaceutical composition of the present disclosure. In events where an infection has occurred within the respiratory tract of a patient, the infection may be treated with a system of the present disclosure. [0122] In some cases, it may be desirable to treat a respiratory infection in a human being’s respiratory tract when a biofilm has already developed. In events where an infection has occurred and a biofilm has developed within the respiratory tract of a patient, the infection may be treated with a method of the present disclosure. In events where an infection has occurred within the respiratory tract of a patient, the infection may be treated with a pharmaceutical composition of the present disclosure. In events where an infection has occurred within the respiratory tract of a patient, the infection may be treated with a system of the present disclosure. [0123] In some cases, a human being may be vulnerable to a respiratory bacterial infection. In some cases, a human being may be immunocompromised. In some cases, a human being may have neutropenia. In some cases, a human being may be HIV positive. In some cases, a human being may be of an old age, wherein old age may be defined as greater than 60 years old. In some cases, a human being may be of a young age, wherein young age may be defined as less than 10 years old. In some cases, a human being may be undergoing another medical treatment, such as chemotherapy. In some cases, a human being may have a lung disease. In some cases, a human being may have a genetic disease. In some cases, a human being may have cystic fibrosis. Inhibition of Respiratory Inflammatory Response [0124] Inflammation response, in some cases, is a result of a natural defensive mechanism of an organism. In some cases, an organism may respond to an irritant (which can be both drugs or pathogens) by increasing blood flow to an area, which can result in redness, increase in temperature, or an increase in swelling at the location of the irritant. In some cases, immune cells of the organisms may concentrate at the location of the irritant. In some cases, immune cells of the organisms may release inflammatory mediators, for example, hormones. In some cases, hormones may include bradykinin and/or histamine. [0125] Though inflammation response can be a natural reaction of a human body to an irritant, in some cases, inflammation can lead to medical complication. Examples of medical conditions that have acute respiratory inflammation effects include pneumonia and acute respiratory distress syndrome Examples of medical conditions that have chronic respiratory inflammation effects include asthma and chronic obstructive pulmonary disease. A lung, as a vital organ in the exchange of gases between the human body and the atmosphere, left untreated in the event of acute inflammation or in a period of chronic inflammation can lead to further medical complications that range from mild to life-threatening in magnitude. In some cases, inflammation within the respiratory system can lead to necrosis of tissue associated with the respiratory system. In some cases, inflammation can lead to mortality in patients. [0126] In some cases, inflammation may be associated or correlated to levels of certain inflammatory biochemical markers. In some cases, the inflammatory biochemical markers may comprise tumor necrosis factor alpha (TNF-α) and/or interleukin-6. In some cases, the inflammatory biochemical markers may comprise a cytokine. In some cases, the inflammatory biochemical markers may comprise interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-11, interleukin-12, interleukin-13, interleukin-14, interleukin-15, interleukin-16, interleukin-17, interleukin-18, interleukin-19, interleukin-20, interleukin-21, interleukin-22, interleukin-23, interleukin-24, interleukin-25, interleukin-26, interleukin-27, interleukin-28, interleukin-29, interleukin-30, interleukin-31, interleukin-32, interleukin-33, interleukin-34, interleukin-35, or interleukin-36. In some cases, the inflammatory biochemical markers may comprise a chemokine, an interferon, or a lymphokine. [0127] In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may inhibit an inflammation response. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may inhibit the levels of one or more inflammatory biochemical markers. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may comprise inhibiting the levels of tumor necrosis factor alpha (TNF-α) and/or interleukin-6. [0128] In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may reduce the rise in an inflammation response. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may reduce the rise in the levels of one or more inflammatory biochemical markers. In some cases, a pharmaceutical composition of the present disclosure, upon administration to at least a portion of a respiratory tract, may reduce the rise in the levels of tumor necrosis factor alpha (TNF-α) and/or interleukin-6. [0129] In some cases, a method present disclosure may inhibit an inflammation response. In some cases, a method present disclosure may inhibit the levels of one or more inflammatory biochemical markers. In some cases, a method present disclosure may inhibit the levels of tumor necrosis factor alpha (TNF-α) and/or interleukin-6. [0130] In some cases, a method present disclosure may reduce the rise in an inflammation response. In some cases, a method present disclosure may reduce the rise in the levels of one or more inflammatory biochemical markers. In some cases, a method present disclosure may reduce the rise in the levels of tumor necrosis factor alpha (TNF-α) and/or interleukin-6. DOSAGE [0131] In some embodiments, the pharmaceutical formulations described herein is in the form of a unit dose. In some embodiments, a pharmaceutical formulation can be formulated to optimize pharmacokinetics/pharmacodynamics of a peptide or salt thereof contained therein. [0132] In some embodiments, a peptide, pharmaceutically acceptable salt thereof, or pharmaceutical formulation comprising a peptide or salt thereof described herein can be administered at a dose of from about 1 mg to about 1000 mg, from about 5 mg to about 1000 mg, from about 10 mg to about 1000 mg, from about 15 mg to about 1000 mg, from about 20 mg to about 1000 mg, from about 25 mg to about 1000 mg, from about 30 mg to about 1000 mg, from about 35 mg to about 1000 mg, from about 40 mg to about 1000 mg, from about 45 mg to about 1000 mg, from about 50 mg to about 1000 mg, from about 55 mg to about 1000 mg, from about 60 mg to about 1000 mg, from about 65 mg to about 1000 mg, from about 70 mg to about 1000 mg, from about 75 mg to about 1000 mg, from about 80 mg to about 1000 mg, from about 85 mg to about 1000 mg, from about 90 mg to about 1000 mg, from about 95 mg to about 1000 mg, from about 100 mg to about 1000 mg, from about 150 mg to about 1000 mg, from about 200 mg to about 1000 mg, from about 250 mg to about 1000 mg, from about 300 mg to about 1000 mg, from about 350 mg to about 1000 mg, from about 400 mg to about 1000 mg, from about 450 mg to about 1000 mg, from about 500 mg to about 1000 mg, from about 550 mg to about 1000 mg, from about 600 mg to about 1000 mg, from about 650 mg to about 1000 mg, from about 700 mg to about 1000 mg, from about 750 mg to about 1000 mg, from about 800 mg to about 1000 mg, from about 850 mg to about 1000 mg, from about 900 mg to about 1000 mg, or from about 950 mg to about 1000 mg. In some embodiments, a peptide, pharmaceutically acceptable salt thereof, or pharmaceutical formulation comprising a peptide or salt thereof described herein can be administered at a dose of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179180, 181, 182, 183, 184, 184, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, or 1000 mg. [0133] In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection can be a concentration from at least about 0.01 µg/mL to at least about 100 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 1 mg/mL to at least about 10 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 0.1 mg/mL to at least about 10 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 1 mg/mL to at least about 100 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about 0.1 mg/mL to at least about 100 mg/mL.In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration from at least about at least about 0.5 mg/mL to at least about 1 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration about 1 mg/mL. In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt is at a concentration about 10 mg/mL. [0134] In some embodiments, pharmaceutical formulation comprising a peptide or pharmaceutically acceptable salt is present at a concentration from at least about 0.01 µg/mL to at least about 100 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt is present at a concentration from at least about at least about 0.1 mg/mL to at least about 5 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt is present at a concentration from at least about at least about 0.5 mg/mL to at least about 1 mg/mL. In some embodiments, the peptide or pharmaceutically acceptable salt is present at a concentration about 1 mg/mL. [0135] In some embodiments, pharmaceutical formulation comprising a peptide or pharmaceutically acceptable salt can exhibit antimicrobial activity against an infection at a concentration from at least about 0.01 µg/mL to at least about 0.02 µg/mL, from at least about 0.02 µg/mL to at least about 0.03 µg/mL, from at least about 0.03 µg/mL to at least about 0.04 µg/mL, from at least about 0.04 µg/mL to at least about 0.05 µg/mL, from at least about 0.05 µg/mL to at least about 0.06 µg/mL, from at least about 0.06 µg/mL to at least about 0.07 µg/mL, from at least about 0.07 µg/mL to at least about 0.08 µg/mL, from at least about 0.08 µg/mL to at least about 0.09 µg/mL, from at least about 0.09 µg/mL to at least about 0.1 µg/mL, from at least about 0.1 µg/mL to at least about 0.2 µg/mL, from at least about 0.2 µg/mL to at least about 0.3 µg/mL, from at least about 0.3 µg/mL to at least about 0.4 µg/mL, from at least about 0.4 µg/mL to at least about 0.5 µg/mL, from at least about 0.5 µg/mL to at least about 0.6 µg/mL, from at least about 0.6 µg/mL to at least about 0.7 µg/mL, from at least about 0.7 µg/mL to at least about 0.8 µg/mL, from at least about 0.8 µg/mL to at least about 0.9 µg/mL, from at least about 0.9 µg/mL to at least about 1 µg/mL, from at least about 1 µg/mL to at least about 2 µg/mL, from at least about 2 µg/mL to at least about 3 µg/mL, from at least about 3 µg/mL to at least about 4 µg/mL, from at least about 4 µg/mL to at least about 5 µg/mL, from at least about 5 µg/mL to at least about 6 µg/mL, from at least about 6 µg/mL to at least about 7 µg/mL, from at least about 7 µg/mL to at least about 8 µg/mL, from at least about 8 µg/mL to at least about 9 µg/mL, from at least about 9 µg/mL to at least about 10 µg/mL, from at least about 10 µg/mL to at least about 20 µg/mL, from at least about 20 µg/mL to at least about 30 µg/mL, from at least about 30 µg/mL to at least about 40 µg/mL, from at least about 40 µg/mL to at least about 50 µg/mL, from at least about 50 µg/mL to at least about 60 µg/mL, from at least about 60 µg/mL to at least about 70 µg/mL, from at least about 70 µg/mL to at least about 80 µg/mL, from at least about 80 µg/mL to at least about 90 µg/mL, from at least about 90 µg/mL to at least about 0.1 mg/mL, from at least about 0.1 mg/mL to at least about 0.2 mg/mL, from at least about 0.2 mg/mL to at least about 0.3 mg/mL, from at least about 0.3 mg/mL to at least about 0.4 mg/mL, from at least about 0.4 mg/mL to at least about 0.5 mg/mL, from at least about 0.5 mg/mL to at least about 0.6 mg/mL, from at least about 0.6 mg/mL to at least about 0.7 mg/mL, from at least about 0.7 mg/mL to at least about 0.8 mg/mL, from at least about 0.8 mg/mL to at least about 0.9 mg/mL, from at least about 0.9 mg/mL to at least about 1 mg/mL, from at least about 1 mg/mL to at least about 2 mg/mL, from at least about 2 mg/mL to at least about 3 mg/mL, from at least about 3 mg/mL to at least about 4 mg/mL, from at least about 4 mg/mL to at least about 5 mg/mL, from at least about 5 mg/mL to at least about 6 mg/mL, from at least about 6 mg/mL to at least about 7 mg/mL, from at least about 7 mg/mL to at least about 8 mg/mL, from at least about 8 mg/mL to at least about 9 mg/mL from at least about 9 mg/mL to at least about 10 mg/mL, from at least about 10 mg/mL to at least about 20 mg/mL, from at least about 20 mg/mL to at least about 30 mg/mL, from at least about 30 mg/mL to at least about 40 mg/mL, from at least about 40 mg/mL to at least about 50 mg/mL, from at least about 50 mg/mL to at least about 60 mg/mL, from at least about 60 mg/mL to at least about 70 mg/mL, from at least about 70 mg/mL to at least about 80 mg/mL, from at least about 80 mg/mL to at least about 90 mg/mL, or from at least about 90 mg/mL to at least about 100 mg/mL. [0136] In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection may be a concentration from at least about 0.01 µg/mL to at least about 0.02 µg/mL, from at least about 0.02 µg/mL to at least about 0.03 µg/mL, from at least about 0.03 µg/mL to at least about 0.04 µg/mL, from at least about 0.04 µg/mL to at least about 0.05 µg/mL, from at least about 0.05 µg/mL to at least about 0.06 µg/mL, from at least about 0.06 µg/mL to at least about 0.07 µg/mL, from at least about 0.07 µg/mL to at least about 0.08 µg/mL, from at least about 0.08 µg/mL to at least about 0.09 µg/mL, from at least about 0.09 µg/mL to at least about 0.1 µg/mL, from at least about 0.1 µg/mL to at least about 0.2 µg/mL, from at least about 0.2 µg/mL to at least about 0.3 µg/mL, from at least about 0.3 µg/mL to at least about 0.4 µg/mL, from at least about 0.4 µg/mL to at least about 0.5 µg/mL, from at least about 0.5 µg/mL to at least about 0.6 µg/mL, from at least about 0.6 µg/mL to at least about 0.7 µg/mL, from at least about 0.7 µg/mL to at least about 0.8 µg/mL, from at least about 0.8 µg/mL to at least about 0.9 µg/mL, from at least about 0.9 µg/mL to at least about 1 µg/mL, from at least about 1 µg/mL to at least about 2 µg/mL, from at least about 2 µg/mL to at least about 3 µg/mL, from at least about 3 µg/mL to at least about 4 µg/mL, from at least about 4 µg/mL to at least about 5 µg/mL, from at least about 5 µg/mL to at least about 6 µg/mL, from at least about 6 µg/mL to at least about 7 µg/mL, from at least about 7 µg/mL to at least about 8 µg/mL, from at least about 8 µg/mL to at least about 9 µg/mL, from at least about 9 µg/mL to at least about 10 µg/mL, from at least about 10 µg/mL to at least about 20 µg/mL, from at least about 20 µg/mL to at least about 30 µg/mL, from at least about 30 µg/mL to at least about 40 µg/mL, from at least about 40 µg/mL to at least about 50 µg/mL, from at least about 50 µg/mL to at least about 60 µg/mL, from at least about 60 µg/mL to at least about 70 µg/mL, from at least about 70 µg/mL to at least about 80 µg/mL, from at least about 80 µg/mL to at least about 90 µg/mL, from at least about 90 µg/mL to at least about 0.1 mg/mL, from at least about 0.1 mg/mL to at least about 0.2 mg/mL, from at least about 0.2 mg/mL to at least about 0.3 mg/mL, from at least about 0.3 mg/mL to at least about 0.4 mg/mL, from at least about 0.4 mg/mL to at least about 0.5 mg/mL, from at least about 0.5 mg/mL to at least about 0.6 mg/mL, from at least about 0.6 mg/mL to at least about 0.7 mg/mL, from at least about 0.7 mg/mL to at least about 0.8 mg/mL from at least about 08 mg/mL to at least about 09 mg/mL from at least about 09 mg/mL to at least about 1 mg/mL, from at least about 1 mg/mL to at least about 2 mg/mL, from at least about 2 mg/mL to at least about 3 mg/mL, from at least about 3 mg/mL to at least about 4 mg/mL, from at least about 4 mg/mL to at least about 5 mg/mL, from at least about 5 mg/mL to at least about 6 mg/mL, from at least about 6 mg/mL to at least about 7 mg/mL, from at least about 7 mg/mL to at least about 8 mg/mL, from at least about 8 mg/mL to at least about 9 mg/mL, from at least about 9 mg/mL to at least about 10 mg/mL, from at least about 10 mg/mL to at least about 20 mg/mL, from at least about 20 mg/mL to at least about 30 mg/mL, from at least about 30 mg/mL to at least about 40 mg/mL, from at least about 40 mg/mL to at least about 50 mg/mL, from at least about 50 mg/mL to at least about 60 mg/mL, from at least about 60 mg/mL to at least about 70 mg/mL, from at least about 70 mg/mL to at least about 80 mg/mL, from at least about 80 mg/mL to at least about 90 mg/mL, or from at least about 90 mg/mL to at least about 100 mg/mL. [0137] In some embodiments, effective amounts of a peptide or pharmaceutically acceptable salt for treating or preventing an infection may be from at least about 1 µL to at least about 2 µL, from at least about 2 µL to at least about 3 µL, from at least about 3 µL to at least about 4 µL, from at least about 4 µL to at least about 5 µL, from at least about 5 µL to at least about 6 µL, from at least about 6 µL to at least about 7 µL, from at least about 7 µL to at least about 8 µL, from at least about 8 µL to at least about 9 µL, from at least about 9 µL to at least about 10 µL, from at least about 10 µL to at least about 20 µL, from at least about 20 µL to at least about 30 µL, from at least about 30 µL to at least about 40 µL, from at least about 40 µL to at least about 50 µL, from at least about 50 µL to at least about 60 µL, from at least about 60 µL to at least about 70 µL, from at least about 70 µL to at least about 80 µL, from at least about 80 µL to at least about 90 µL, from at least about 90 µL to at least about 100 µL, from at least about 100 µL to at least about 200 µL, from at least about 200 µL to at least about 300 µL, from at least about 300 µL to at least about 400 µL, from at least about 400 µL to at least about 500 µL, from at least about 500 µL to at least about 600 µL, from at least about 600 µL to at least about 700 µL, from at least about 700 µL to at least about 800 µL, from at least about 800 µL to at least about 900 µL, from at least about 900 µL to at least about 1 mL, from at least about 1 mL to at least about 2 mL, from at least about 2 mL to at least about 3 mL, from at least about 3 mL to at least about 4 mL, from at least about 4 mL to at least about 5 mL, from at least about 5 mL to at least about 6 mL, from at least about 6 mL to at least about 7 mL, from at least about 7 mL to at least about 8 mL, from at least about 8 mL to at least about 9 mL, from at least about 9 mL to at least about 10 mL, from at least about 10 mL to at least about 20 mL, from at least about 20 mL to at least about 30 mL, from at least about 30 mL to at least about 40 mL, from at least about 40 mL to at least about 50 mL from at least about 50 mL to at least about 60 mL from at least about 60 mL to at least about 70 mL, from at least about 70 mL to at least about 80 mL, from at least about 80 mL to at least about 90 mL, from at least about 90 mL to at least about 100 mL, from at least about 100 mL to at least about 200 mL, from at least about 200 mL to at least about 300 mL, from at least about 300 mL to at least about 400 mL, from at least about 400 mL to at least about 500 mL, from at least about 500 mL to at least about 600 mL, from at least about 600 mL to at least about 700 mL, from at least about 700 mL to at least about 800 mL, from at least about 800 mL to at least about 900 mL, from at least about 900 mL to at least about 1 L, from at least about 1 L to at least about 2 L, from at least about 2 L to at least about 3 L, from at least about 3 L to at least about 4 L, from at least about 4 L to at least about 5 L, from at least about 5 L to at least about 6 L, from at least about 6 L to at least about 7 L, from at least about 7 L to at least about 8 L, from at least about 8 L to at least about 9 L, from at least about 9 L to at least about 10 L, from at least about 10 L to at least about 20 L, from at least about 20 L to at least about 30 L, from at least about 30 L to at least about 40 L, from at least about 40 L to at least about 50 L, from at least about 50 L to at least about 60 L, from at least about 60 L to at least about 70 L, from at least about 70 L to at least about 80 L, from at least about 80 L to at least about 90 L, from at least about 90 L to at least about 100 L, from at least about 100 L to at least about 200 L, from at least about 200 L to at least about 300 L, from at least about 300 L to at least about 400 L, from at least about 400 L to at least about 500 L, from at least about 500 L to at least about 600 L, from at least about 600 L to at least about 700 L, from at least about 700 L to at least about 800 L, from at least about 800 L to at least about 900 L, from at least about 900 L to at least about 1 kL, from at least about 1 kL to at least about 2 kL, from at least about 2 kL to at least about 3 kL, from at least about 3 kL to at least about 4 kL, from at least about 4 kL to at least about 5 kL, from at least about 5 kL to at least about 6 kL, from at least about 6 kL to at least about 7 kL, from at least about 7 kL to at least about 8 kL, from at least about 8 kL to at least about 9 kL, or from at least about 9 kL to at least about 10 kL. KITS [0138] Disclosed herein are kits. A kit can comprise a pharmaceutical composition comprising a peptide, or pharmaceutically acceptable salt thereof, and an excipient. A method can further comprise an inclusion of instructions for use. In some embodiments, instructions for use can direct administration of a unit dose of a pharmaceutical composition to a subject. In some cases, the kits include separate containers/receptacles for containing the pharmaceutical composition as described herein. In some other cases, the kits include a single container for containing the pharmaceutical composition. The kits can further include instructions for methods of using the kit The instructions for use of the kit can comprise instructions for use of the pharmaceutical composition and the aerosolization device (e.g., a nebulizer, dry powder inhaler, aerosolization device) to treat or prevent lung disease or injury. In some embodiments, the kit disclosed herein comprises a pharmaceutical composition disclosed herein. In some embodiments, the pharmaceutical composition of the kit disclosed herein further comprises an excipient, pH buffering or adjusting agent. In some embodiments, the kit comprises a pharmaceutical composition that is a dry powder. In some embodiments, the kit comprises a pharmaceutical composition that is a liquid. In some embodiments, the kit comprises a pharmaceutical composition that is an aerosol. In some embodiments, the kit comprises a pharmaceutical composition whose pH is between 4.5 and 6.5. In some embodiments, the kit comprises a pharmaceutical composition whose osmolality is between at least 270 mOsm/kg to at least 350 mOsm/kg. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is acetate. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is mannitol. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is trehalose. In some embodiments, the kit comprises a pharmaceutical composition whose excipient is human serum albumin. In some embodiments, the pharmaceutical composition of the kit comprises an antibiotic. In some embodiments, the pharmaceutical composition of the kit comprises a neutrophil elastase. In some embodiments, the pharmaceutical composition of the kit comprises a lung surfactant. [0139] Disclosed herein are inhaler kits. An inhaler kit can comprise a pharmaceutical composition comprising a peptide disclosed herein or a pharmaceutically acceptable salt thereof and an excipient. A method can further comprise an inclusion of instructions for use. In some embodiments, instructions for use can direct administration of a unit dose of a pharmaceutical composition to a subject. In some cases, the inhaler kits include separate containers/receptacles for containing the pharmaceutical composition as described herein. In some other cases, the inhaler kits include a single container for containing the pharmaceutical composition. The inhaler kits can further include instructions for methods of using the inhaler kit. The instructions for use of the inhaler kit can comprise instructions for use of the pharmaceutical composition and the aerosolization device (e.g., a nebulizer, dry powder inhaler, aerosolization device) to treat or prevent lung disease or injury. In some embodiments, the inhaler kit disclosed herein comprises a pharmaceutical composition disclosed herein. In some embodiments, the pharmaceutical composition disclosed herein further comprises an excipient, pH buffering or adjusting agent. In some embodiments, the inhaler kit comprises a pharmaceutical composition that is a dry powder. In some embodiments, the inhaler kit comprises a pharmaceutical composition that is a liquid. In some embodiments, the inhaler kit comprises a pharmaceutical composition that is an aerosol. In some embodiments the inhaler kit comprises a pharmaceutical composition whose pH is between 4.5 and 6.5. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose osmolality is between at least 270 mOsm/kg to at least 350 mOsm/kg. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is acetate. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is mannitol. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is trehalose. In some embodiments, the inhaler kit comprises a pharmaceutical composition whose excipient is human serum albumin. In some embodiments, the pharmaceutical composition of the inhaler kit comprises an antibiotic. In some embodiments, the pharmaceutical composition of the inhaler kit comprises a neutrophil elastase. In some embodiments, the pharmaceutical composition of the inhaler kit comprises a lung surfactant. TERMINOLOGY [0140] As used herein, the term “about” or “approximately” can mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean plus or minus 10%, per the practice in the art. Alternatively, “about” can mean a range of plus or minus 20%, plus or minus 10%, plus or minus 5%, or plus or minus 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, or within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed. Also, where ranges and/or subranges of values are provided, the ranges and/or subranges can include endpoints of the ranges and/or subranges. [0141] The use of numerical values in the various ranges specified in this application, unless expressly indicated otherwise, are stated as approximations as though the minimum and maximum values within the stated ranges are both preceded by the word "about". In this manner, slight variations above and below the stated ranges can be used to achieve substantially the same results as values within the ranges. Also, unless indicated otherwise, the disclosure of these ranges is intended as a continuous range including every value between the minimum and maximum values. For definitions provided herein, those definitions also refer to word forms, cognates and grammatical variants of those words or phrases. [0142] As used herein, the terms “biofilm”, “microbial film”, “microbial biofilm”, “bacterial film”, refers to any film comprising microorganisms and their excretions. [0143] As used herein, the terms “comprising,” “comprise” or “comprised,” and variations thereof in reference to elements of an item formulation apparatus method process system claim etc. are intended to be open-ended, meaning that the item, formulation, apparatus, method, process, system, claim etc. includes those elements and other elements can be included and still fall within the scope/definition of the described item, formulation, apparatus, method, process, system, claim etc. As used herein, "a" or "an" means one or more. As used herein "another" may mean at least a second or more. [0144] As used herein, the term “object” refers to any object with a surface. Some embodiments in the present disclosure may be applied to the surface of an object to prevent or to treat microbial biofilm. In some embodiments, the object can a solid object, a liquid object, a hard object, a soft object, a metallic object, a polymeric object, a ceramic object, a composite object, a biological object, members of the animal kingdom, a human being, a biological transplant object, a replaced joint, or any other object with a surface on which some of the disclosed methods and the formulations can be applied. [0145] As used herein, the terms "patient" or "subject" generally refer to any individual that has, may have, or may be suspected of having a disease condition (e.g., a bacterial infection). In some embodiments, the bacterial infection may be caused by surgeries, physical wounds, etc. The subject may be an animal. The animal can be a mammal, such as a human, non-human primate, a rodent such as a mouse or rat, a dog, a cat, pig, sheep, or rabbit. Animals can be fish, reptiles, or others. Animals can be neonatal, infant, adolescent, or adult animals. The subject may be a living organism. The subject may be a human. Humans can be greater than or equal to 1, 2, 5, 10, 20, 30, 40, 50, 60, 65, 70, 75, 80 or more years of age. A human may be from about 18 to about 90 years of age. A human may be from about 18 to about 30 years of age. A human may be from about 30 to about 50 years of age. A human may be from about 50 to about 90 years of age. The subject may have one or more risk factors of a condition and be asymptomatic. The subject may be asymptomatic of a condition. The subject may have one or more risk factors for a condition. The subject may be symptomatic for a condition. The subject may be symptomatic for a condition and have one or more risk factors of the condition. The subject may have or be suspected of having a disease, such as an infection. The subject may be a patient being treated for a disease, such as an infection. The subject may be predisposed to a risk of developing a disease such as a bacterial infection. The subject may be in remission from a disease, such as a bacterial infection. The subject may not have a bacterial infection. The subject may be healthy. [0146] As used herein, a “pharmaceutically acceptable excipient”, “aqueous carrier” or “pharmaceutically acceptable aqueous carrier” refer to solvents or dispersion media, and the like, that are physiologically compatible and known to those skilled in the art. Examples of pharmaceutically acceptable carriers include one or more of water, saline, phosphate buffered saline dextrose glycerol ethanol and the like as well as combinations thereof Pharmaceutically acceptable carriers may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the active agent. [0147] As used herein, “Tween® 80” refers to polysorbate 80 or polyethylene glycol sorbitan monooleate. [0148] As used herein, a “effective amount” of an active agent can refer to an amount that is effective to achieve a desired result. An effective amount of a given active agent can vary with respect to factors such as the type and severity of the disorder or disease being treated and the age, gender, and weight of the patient. [0149] The term “homology” can refer to a % identity of a polypeptide to a reference polypeptide. As a practical matter, whether any particular polypeptide can be at least 50%, 60%, 70%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to any reference amino acid sequence of any polypeptide described herein (which may correspond with a particular nucleic acid sequence described herein), such particular polypeptide sequence can be determined conventionally using known computer programs such the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis.53711). When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence according to the present invention, the parameters can be set such that the percentage of identity is calculated over the full length of the reference amino acid sequence and that gaps in homology of up to 5% of the total number of amino acid residues in the reference sequence are allowed. [0150] For example, in a specific embodiment the identity between a reference sequence (query sequence, i.e., a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, may be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci.6:237-245 (1990)). In some embodiments, parameters for a particular embodiment in which identity is narrowly construed, used in a FASTDB amino acid alignment, can include: Scoring Scheme=PAM (Percent Accepted Mutations) 0, k-tuple=2, Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter. According to this embodiment, if the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction can be made to the results to take into consideration the fact that the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity. For subject sequences truncated at the N- and C-termini, relative to the query sequence, the percent identity can be corrected by calculating the number of residues of the query sequence that are lateral to the N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. A determination of whether a residue is matched/aligned can be determined by results of the FASTDB sequence alignment. This percentage can be then subtracted from the percent identity, calculated by the FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score can be used for the purposes of this embodiment. In some embodiments, only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence are considered for this manual correction. For example, a 90 amino acid residue subject sequence can be aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequence are manually corrected for. [0151] The terms “co-administration”, “administered in combination with” and their grammatical equivalents or the like, as used herein, can encompass administration of selected therapeutic agents to a subject, and can include treatment regimens in which agents are administered by the same or different route of administration or at the same or different times. In some embodiments, a peptide disclosed herein can be co-administered with other agents. These terms can encompass administration of two or more agents to a subject so that both agents and/or their metabolites are present in the subject at the same time. They can include simultaneous administration, administration at different times, and/or administration in a formulation in which both agents are present Thus in some embodiments a peptide and an additional agent(s) can be administered in a single formulation. In some embodiments, a peptide and an additional agent(s) can be admixed in the formulation. In some embodiments, a same peptide or agent can be administered via a combination of different routes of administration. In some embodiments, each agent administered can be in a therapeutically effective amount. EXAMPLES [0152] The following examples are provided to further illustrate some embodiments of the present disclosure, but are not intended to limit the scope of the disclosure; it will be understood by their exemplary nature that other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used. Example 1: SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination in the presence and absence of neutrophil elastase [0153] This example illustrates the determination of the in vitro activity of eCAPs, SEQ ID NO: 17 and SEQ ID NO: 1, compared to other antimicrobial agents in the presence of neutrophil elastase against contemporary, clinically relevant respiratory bacteria, including MDR and XDR strains and isolates of P. aeruginosa, S. maltophilia, B. cepacia, A. xylosoxidans, and MRSA, from patients with cystic fibrosis (CF). Minimum inhibitory concentration (MIC) testing will be conducted in both cation-adjusted Mueller Hinton broth (CAMHB) and Roswell Park Memorial Institute (RPMI) media. Cytotoxicity, mucociliary escalator function, tight junction integrity and membrane potential will be measured to assess the effects of the peptides. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the presence of neutrophil elastase against contemporary, clinically relevant respiratory bacteria from patients with CF. [0154] The Di et al. (2020) protocol is used to study SEQ ID NO: 17 and SEQ ID NO: 1 in the presence of neutrophil elastase. This protocol has advantages in that because it was specifically used in studying the stability of other antimicrobial peptides in the presence of neutrophil elastase. The in vitro activity (MIC determination) of SEQ ID NO: 17 and SEQ ID NO: 1 against contemporary, clinically relevant respiratory bacteria from individuals with CF will be determined by serial dilutions of human neutrophil elastase against a range of concentrations of SEQ ID NO: 17 and SEQ ID NO: 1. Reagents [0155] Human neutrophil elastase (HNE) (Elastin Products Company, Owensville, MO), neutrophil elastase-specific chromogenic substrate (Elastin Products Company, Owensville, MO) DNase (Pulmozyme) CAMHB and RPMI-1640 (Hyclone) and 0002% P-80 (Amresco) will be used. For MIC assessment, the stock solution of SEQ ID NO: 17 and SEQ ID NO: 1 will be freshly prepared at 20x, 0.64 mg/mL, in DPBS containing 0.002% P-80. The 11-point dilutions of SEQ ID NO: 17 and SEQ ID NO: 1 will be carried out using DPBS with 0.002% P- 80. Bacteria [0156] The P. aeruginosa and S. aureus strains for MIC testing of this study will be obtained from the American Type Culture Collection (ATCC; S. aureus ATCC 29213) and the FDA CDC AR Isolate Bank (P. Aeruginosa AR-BANK#0246 and P. aeruginosa AR-BANK#0266). Susceptibility is summarized in Table 2 and will be determined following the Clinical Laboratory Standards Institute (CLSI) M07-A10 microdilution procedure and the CLSI M100 interpretive criteria. The species identity was confirmed with 16S analysis. The antimicrobial resistance genes of each strain, Table 1, were provided by the AR Isolate bank website and were identified from whole genome sequence analysis using the ResFinder tool. [0157] Table 2. P. aeruginosa and S. aureus strains for MIC studies, antibiotic susceptibility. S denotes susceptible, R denotes resistant or not susceptible, and I denotes intermediate susceptibility based on the CLSI interpretive criteria published in CLSI M100. Colistin susceptibility is based on EUCAST breakpoints. Asterisk (*) denotes that P. aeruginosa strain ATCC 27853 will be used as the quality control strain for MIC assay. A G P A C
Figure imgf000052_0001
Ceftazidime 1 S >64 R 16 I-R Ceftazidime/avibactam 2/4 S >16/4 R 2/4 S I C C T
Figure imgf000053_0001
Neutrophil Elastase Inhibition of Activity Assay [0158] In order to determine whether HNE inactivates the in vitro antimicrobial activity of SEQ ID NO: 1 or SEQ ID NO: 17, plates 1 and 2 of HNE (1 - 4 µM) will be mixed with 0.03 - 32 µg/mL of either SEQ ID NO: 1 or SEQ ID NO: 17 in 1X phosphate buffered saline (PBS) in checkerboard fashion in a 96-well microplate and incubated in a humidified chamber for 1 hour at 37 °C. In order to confirm that HNE is active under these conditions, Plates 3 and 4 will be created to be identical to Plates 1 and 2 but will also receive 75 µL of a neutrophil elastase- specific chromogenic substrate, which comprises 0.8 mM methoxysuccinyl-AAPV-P- nitroanalide in 0.1 M Tris-HCl (tris[hydroxymethyl] aminomethane–hydrochloride)/0.15 M sodium chloride (NaCl) (pH 7.5). After both plates are incubated for 1 hour at 37 °C, the reaction will be stopped with 40 µL of 50 µM soybean trypsin inhibitor in 0.1 M Tris-HCl/0.15 M NaCl (pH 7.5). After assaying Plates 3 and 4 to confirm that HNE was active under the experimental conditions, the wells from Plate 1 and Plate 2 (HNE treated SEQ ID NO: 1 or SEQ ID NO: 17) will be utilized as the source of antimicrobial peptide in a broth microdilution MIC assay with cation-adjusted Mueller Hinton broth (CAMHB) or RPMI-1640 as the broth medium. Both media will be supplemented with 0.002% P-80 for testing of SEQ ID NO: 17 and SEQ ID NO: 1. The MIC (µg/mL) will be read and recorded as the lowest concentration of drug that inhibited visible growth of the organisms listed above. Appropriate QC antibiotics and strains will be included to validate the assay. Pulmozyme Inhibition of Activity Assay [0159] Similar to the methodology described for HNE above, SEQ ID NO: 1 and SEQ ID NO: 17 will be incubated with various concentrations of Pulmozyme (0.5 - 16 µM) and subsequently added to the MIC assay using the P. aeruginosa and S. aureus strains listed in Table 2. [0160] The data expected to be obtained will be biological activity (MIC determination) of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of neutrophil elastase. The data will be analyzed and interpreted by comparing the MIC of SEQ ID NO: 17 and SEQ ID NO: 1 to the same bacteria in the presence and absence of neutrophil elastase. Example 2: SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination in the presence and absence of surfactant [0161] This example illustrates the determination of the in vitro activity of eCAPs, SEQ ID NO: 17 and SEQ ID NO: 1, compared to other antimicrobial agents in the presence of surfactant (Survanta®) against contemporary, clinically relevant respiratory bacteria, including MDR and XDR strains and isolates of P. aeruginosa, S. maltophilia, B. cepacia, A. xylosoxidans, and MRSA, from patients with cystic fibrosis (CF). Minimum inhibitory concentration (MIC) testing will be conducted in both cation-adjusted Mueller Hinton broth (CAMHB) and RPMI media. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the presence of surfactant against contemporary, clinically relevant respiratory bacteria from patients with CF. [0162] Because some antibacterial drugs may be inactive when protein bound or there may be insufficient free active drug at trough concentrations, the effects, if any, of surfactant on the in vitro activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be determined. The Huang et al. (2018) protocol will be used to study SEQ ID NO: 17 and SEQ ID NO: 1 in the presence of surfactant. Cytotoxicity, mucociliary escalator function, tight junction integrity and membrane potential will be measured to assess the effects of the peptides. MIC Assay in the Presence of Surfactant [0163] SEQ ID NO: 17 and SEQ ID NO: 1 will be tested in an 11-point titration from 0.032 to 32 µg/mL with and without Survanta® (0, 2.5, 5, and 10%) in RPMI medium. All tests will be performed in duplicate. The method for preparing medium, inoculum and the reading of MIC values will follow the guidelines of CLSI M07-A10 (2020). [0164] The direct colony suspension method will be used to prepare inoculated broth. Isolated colonies will be taken from an 18–24 h culture plate and resuspended in 2 mL saline solution (0.9% NaCl) and adjusted to OD620nm 0.085, which is equivalent to 0.5 McFarland standard (OD620nm range 0.085 to 0.088). The bacterial suspension of OD620nm 0.085 corresponds to approximate 1.5 x 108 CFU/mL; and will be subsequently diluted to reach the final bacterial count of approximately 5 x 105 CFU/mL with a range of 2–8 x 105 CFU/mL. SEQ ID NO: 17 and SEQ ID NO: 1 will be tested in an 11-point titration from 0.032 to 32 µg/mL with 0%, 2.5%, 5% and 10% (v/v) of Survanta® in RPMI medium as described below and shown in FIG.1. [0165] Assay plates will be incubated at 37 °C for 18 h. The test plate will be visually examined and each well will be visually scored for growth or complete inhibition of growth then the MIC is recorded. The MIC endpoint is the lowest concentration that results in 100% visual growth inhibition. The duplicate assays may yield the same MIC value. If the values differ, the higher MIC value will be reported. [0166] A control compound dilution plate will be included to observe precipitate in the test medium that is not inoculated. The compound dilution will be generated in RPMI with or without Survanta® as the same concentrations as the MIC assay plate. The control plate will be incubated at 37°C for 18 h. The test plate will be visually examined and each well will be visually scored for precipitate with results reported. [0167] The data expected to be obtained is the biological activity (MIC determination) of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of surfactant. The data will be analyzed and interpreted by comparing the MIC of SEQ ID NO: 17 and SEQ ID NO: 1 to the same bacteria in the presence and absence of surfactant. [0168] Pseudomonas aeruginosa, methicillin-resistant S. aureus, S. maltophilia, B. cepacia, and A. xylosoxidans are bacteria that can be found in airway secretions of individuals with CF. These bacteria may be multidrug resistant to standard of care antibiotics. The in vitro activity of SEQ ID NO: 17 and SEQ ID NO: 1 and other antimicrobials against these bacteria will be determined in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI 2020). Example 3: SEQ ID NO: 17 and SEQ ID NO: 1 MIC Determination in the presence of CAMHB and RPMI [0169] This example illustrates the determination of the in vivo activity, including respiratory track tolerability / toxicity, toxicokinetics and efficacy, of SEQ ID NO: 17 and SEQ ID NO: 1 in animals. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may have in vitro activity in the standard test medium CAMHB as well as in RPMI medium, which may support better solubility, against contemporary, clinically relevant respiratory bacteria from patients with CF. Bacteria [0170] Contemporary, clinical respiratory bacteria consisting of P. aeruginosa [N=50], S. maltophilia [N=50], B. cepacia [n=50], A. xyloxidans [N=50], and MRSA [N=50]) from individuals with CF will be studied for SEQ ID NO: 17 and SEQ ID NO: 1 MIC determination. These bacteria will be reference strains from the American Type Culture Collection (ATCC; Manassas, VA), the Centers for Disease Control Antibiotic Resistance Bank (CDC, Atlanta, GA) and clinical isolates from the Micromyx repository (MMX; Kalamazoo MI) MIC Assay in the presence of CAMHB and RPMI [0171] The in vitro activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be determined by broth microdilution MIC testing in CAMHB and RPMI in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI 2020). The comparators will include imipenem, levofloxacin, tigecycline, linezolid, vancomycin, oxacillin, ceftazidime, colistin, and amikacin. Media employed for testing in the broth microdilution MIC assay for all organisms will be cation-adjusted Mueller Hinton broth (MHBII; Becton Dickinson) and RPMI-1640 medium (Hyclone) with MOPS (EMD Millipore). Both media will be supplemented with 0.002% P-80 (Amresco) for testing of SEQ ID NO: 17 and SEQ ID NO: 1. The MIC (µg/mL) will be read and recorded as the lowest concentration of drug that inhibits visible growth of the organism. MIC50/90 values and ranges will be reported, MIC and cumulative distributions of SEQ ID NO: 17 and SEQ ID NO: 1 will be reported against strain and isolates tested. Antibiotic susceptibilities will be interpreted using current CLSI susceptibility breakpoint criteria (M100, 2020). [0172] The data expected to be obtained is MIC determination of SEQ ID NO: 17 and SEQ ID NO: 1 to contemporary, clinically relevant respiratory bacteria in the presence and absence of surfactant. The data will be analyzed and interpreted by comparing the MIC of SEQ ID NO: 17 and SEQ ID NO: 1 to the same bacteria in the presence and absence of surfactant. No potential difficulties and/or limitations of the proposed procedure are anticipated to achieve this aim. Example 4: SEQ ID NO: 17 and SEQ ID NO: 1 respiratory track tolerability / toxicity and toxicokinetics in rats [0173] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals. [0174] This example illustrates the determination of respiratory tract tolerability / toxicity and toxicokinetics of SEQ ID NO: 17 and SEQ ID NO: 1 in rats. In vitro complex cellular systems will be used to evaluate respiratory track tolerability. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may be tolerable and may have minimal respiratory track toxicity in rats. [0175] Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy [0176] Table 3. Study design for an Escalating and 7-Day Range Finding Inhalation Toxicity Study in Rats. Compliance: Non-GLP S D D F D R A I P
Figure imgf000057_0001
[0177] Table 4. Test system groups for Example 4. Asterisk (*) denotes that additional animals in Groups 5-8 will be used for Toxicokinetic sample collections.
Figure imgf000057_0002
8 (Repeat Dose) TBD 5+6 5+6 [0178] Table 5. Test system group details for Example 4. S T A
Figure imgf000057_0003
Source: Charles River Pretreatment Period: Two weeks D B o F C T C ll t T B T s .
Figure imgf000058_0001
( on ro an g ose) (o er ssues re a ne ). Example 5: SEQ ID NO: 17 and SEQ ID NO: 1 respiratory track tolerability / toxicity and toxicokinetics in monkeys [0179] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals. [0180] This example illustrates the determination of respiratory tract tolerability / toxicity and toxicokinetics of SEQ ID NO: 17 and SEQ ID NO: 1 in monkeys. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may be tolerable and may have minimal respiratory track toxicity in monkeys. [0181] Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy. [0182] Table 6. Study design for an Escalating and 7-Day Range Finding Inhalation Toxicity Study in Monkeys. C li N GLP S D D F D . R A I P
Figure imgf000059_0001
. [0183] Table 7. Test system groups for Example 5.
Figure imgf000059_0002
5 (Repeat Dose) TBD 1 1 [0184] Table 8. Test system group details for Example 5. S
Figure imgf000059_0003
Total Population: 5/sex on study; 6/sex ordered Age: 2-3 years or 2.5-4 kg on arrival S P D B F C y T C A T T s
Figure imgf000060_0001
. Example 6: A Single Dose PK and BALPF Collection Inhalation Toxicity Study in Monkeys [0185] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals. [0186] This example illustrates the determination of pharmacokinetics (PK) of SEQ ID NO: 17 and SEQ ID NO: 1 and their effects on bronchoalveolar pulmonary lavage fluid (BALPF) in monkeys. [0187] Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy. [0188] Table 9. Study design for a Single Dose PK and BALPF Collection Inhalation Toxicity Study with Monkeys. Compliance: Non-GLP S D D F 6 D R A I P
Figure imgf000061_0001
[0189] Table 10. Test system groups for Example 6.
Figure imgf000061_0002
[0190] Table 11. Test system group details for Example 6. S T A S P D B F T C
Figure imgf000061_0003
Sponsor-designated US laboratory for PK analysis Toxicokinetic Evaluation: By the CRO/vendor T y
Figure imgf000062_0001
Example 7: A 14-Day Inhalation Toxicity Study in Sprague Dawley Rats Followed by a 28- Day Recovery [0191] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals. [0192] This example illustrates the determination of toxicity of SEQ ID NO: 17 and SEQ ID NO: 1 in rats. In some cases, SEQ ID NO: 17 and SEQ ID NO: 1 may show efficacy in a murine lung infection model. [0193] Table 12. Study design for a 14-Day Inhalation Toxicity Study in Sprague Dawley Rats Followed by a 28-Day Recovery. C S D D F e D R A I P
Figure imgf000062_0002
part c e s ze anays s. Table 13. Test system groups for Example 7. Asterisk (*) denotes 10/sex/Groups 1 to 4 necropsied 24-hours following the last dose, the remaining 5/sex/Groups 1 and 4 (recovery) ne i d 4 k f ll i h l d
Figure imgf000062_0003
4 TBD 10+5 10+5 18 18 [0194] Table 14. Test system group details for Example 7. Spares: 10/sex T A S P D C B F O f a C K T C T T r
Figure imgf000063_0001
ose groups an ecovery an ma s, preserve n xat ve Example 8: A 14-Day Inhalation Toxicity Study in Cynomolgus Monkeys Followed by a 28- Day Recovery [0195] Because the airways of individuals with CF may be intolerant to peptides and/or inhospitable to the stability of peptides given the presence of enzymes that may degrade an inhaled peptide, the in vivo activity of SEQ ID NO: 17 and SEQ ID NO: 1 will be studied in animals. [0196] This example illustrates the determination of toxicity of SEQ ID NO: 17 and SEQ ID NO: 1 in monkeys. [0197] Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy. [0198] Table 15. Study design for a 14-Day Inhalation Toxicity Study in Cynomolgus Monkeys Followed by a 28-Day Recovery. Compliance: GLP S D D F e D R A I P
Figure imgf000064_0001
[0199] Table 16. Test system groups for Example 8.
Figure imgf000064_0002
[0200] Table 17. Test system group details for Example 8. S T A S P D C B
Figure imgf000064_0003
Food Consumption: Daily.
Figure imgf000065_0001
Example 9: SEQ ID NO: 17 and SEQ ID NO: 1 efficacy in a murine Pseudomonas aeruginosa extended lung infection model - Tolerability/PK Assessment
[0201] The tolerability analysis will be conducted to determine the upper limit of SEQ ID NO: 17 and SEQ ID NO: 1 dosage to neutropenic mice. SEQ ID NO: 17 and SEQ ID NO: 1 will be intratracheally (IT) administered with the dose schedule and concentrations indicated in the Table 18 study design and FIG. 2, top panel. Doses will be intratracheally (IT) or subcutaneously (SC) administered twice per day (BID) with 12 h intervals (ql2h) for five consecutive days. Side effects associated with overt toxicity will be monitored 30 minutes after each dose administration. Mortality and body weight will be observed and recorded daily for each treatment day until sacrifice time point. Neutropenic male ICR mice will be used for the tolerability/PK study. The animals will not be infected. Two bio samples, plasma and BALF, will be collected at up to 8 time points after the last dose administration (after BID ql2h x 5 days), 3 animals per time point. Plasma will be collected at 0.25, 2, 12, 24, 48, 72, 96, 120 hours (h) post-treatment.
[0202] Toxicokinetic and standard PK assessment for the peptide will be made both systemically (plasma/serum) and in BALF. The distribution in the lung will be assessed by measurement of the peptide concentrations in BALF and tissue. Further assessments will be made using radiolabeled peptide and lung tissue scintigraphy.
Therapeutic Compounds [0203] The dose concentrations for animal administration are shown in Table 19 for the tolerability/PK study. The SEQ ID NO: 17 and SEQ ID NO: 1 solution will be freshly formulated in DPBS on the first dosing day, and stored at 4°C, protected from light. Dulbecco’s phosphate buffered saline (DPBS) is purchased as 10x stock, and dilution will be conducted with WFI to reach 1x concentration for vehicle in MIC and animal studies. The formulation will be visually inspected to note heterogeneity. [0204] Table 18. Study design for tolerability and pharmacokinetics assessment with mice. D Mice e
Figure imgf000066_0001
Animal Preparation [0205] The tolerability/PK assessment will be conducted with male ICR mice, 5-6 weeks of age, weighing 22 ± 2 g. Animals will be immunosuppressed by two intraperitoneal injections of cyclophosphamide, the first at 150 mg/kg 4 days before treatment (Day –4) and the second at 100 mg/kg 1 day before treatment (Day –1), prior to treatment on Day 0. PDS determined in prior complete blood count studies that this cyclophosphamide treatment schedule resulted in neutropenia (< 100 neutrophils per µL) until Day 2 after treatment. [0206] For longer duration observations, more than 3 days, cyclophosphamide (CP) will be administered by additional IP injections to render the animals persistently neutropenic over the five-day duration of study (Gumbo et. al., 2007) and up to 120 h collection time point (Table 2 study design and Figure 2, top panel). The first CP dose, 150 mg/kg, will be administered at four days before treatment (Day –4); the second, 100 mg/kg, 24 h before treatment (Day –1) prior to treatment on Day 0, the third and ongoing CP doses will be at 100 mg/kg on Day +1, Day +3, Day +5 and Day +7. PDS determined in prior complete blood count studies that this cyclophosphamide treatment schedule resulted in persistent neutropenia (< 100 neutrophils per µL) until Day 8 after treatment (data not shown). Treatment and evaluation [0207] The test article, SEQ ID NO: 17 and SEQ ID NO: 1, will be administered to animals by intratracheal (IT) administration using the dose schedule, volumes, and concentrations indicated in Table 18 for tolerability/PK evaluation. Animals will be deeply anesthetized with isoflurane (3%-5%). The mouse will be held upright and a 22 G long blunt needle will be directly inserted into the trachea, and then 20 µL of test article solution will be injected directly into the trachea. The mouse will be held in the upright position for about 15 seconds and then placed into the cage for recovery. Animals will be observed at 30 min after dosing to detect acute toxicity which will be recorded and reported, if observed. Animals will be humanely euthanized if severe acute toxicity is observed. Side effect examinations [0208] Animals will be observed for the presence of acute toxic symptoms and autonomic effects after 30 minutes of each IT administration. These observations include: gait, posture, ruffled fur, immobility, mucous membrane, salivation, tremors, convulsions, reactivity to handling, respiratory, stool, and mortality. Body weight and mortality will be observed and recorded daily for each treatment day until sacrifice time point. Animals will be humanely euthanized at earlier time points if they are found to be in distress or a moribund state. Plasma and BALF collection [0209] Two biosamples, plasma and BALF will be collected. The collection time points are at 0.25, 2, 12, 24, 48, 72, 96, 120 hours (h) post-treatment. The collected samples will be frozen and shipped to the bioanalytical CRO to be designated by Peptilogics. [0210] Plasma collection. Terminal blood collection from cardiac puncture will be conducted under CO2 euthanasia. Blood, 0.3-0.4 mL, will be drawn into tubes coated with K2EDTA, mixed gently and kept on ice and centrifuged at 2,500 ×g for 15 minutes at 4°C within 1 hour of collection. The plasma will be harvested and kept frozen at -80°C until further processing. [0211] To collect BALF, 0.5 mL of PBS will be administered once through a tracheal cannula after which about 0.2 to 0.3 mL of BALF will be obtained. The BALF will be kept on ice and centrifuged at 2,500 ×g for 15 minutes at 4°C within 1 hour of collection. The supernatant will be collected and kept frozen at -80°C. Example 10: SEQ ID NO: 17 and SEQ ID NO: 1 efficacy in a murine Pseudomonas aeruginosa extended lung infection model - Efficacy Assessment: Extended Lung Infection Model [0212] Efficacy analysis will be conducted with neutropenic mice. Animals will be intranasally (IN) infected with pathogen suspension into the lung. Test article, SEQ ID NO: 17 and SEQ ID NO: 1 and amikacin, will be IT and SC administered, respectively, with the dose schedule and concentrations indicated in the Table 19-21 study design and FIG.2 scheme, bottom panel. SEQ ID NO: 17 and SEQ ID NO: 1 will be IT administered first followed by SC administration of amikacin within 5 minutes (no in vitro antagonism has been observed on checkerboard assay between SEQ ID NO: 17 and SEQ ID NO: 1 with amikacin). Doses will be administered twice at 12 h intervals (BID q12h) for five consecutive days starting at 12 h post-infection. Animals will be humanely euthanized at 12, 36 and 120 h after infection. Lung tissue will be recovered, and pathogen burden will be enumerated with the dilution plating technique. Bacterial burden (CFU/g tissue) of test article treated animal groups will be compared to the baseline bacterial count at 12 h after infection and the difference in counts (Δ) will be reported. Significance of effects will be assessed with ANOVA. [0213] The doses will be determined after completion of the tolerability/PK study of Example 8. [0214] Groups 3 and 8. Control reference agent, amikacin 1000 mg/kg, will be subcutaneously (SC) administered twice (BID) daily with a 12 h interval (q12h) starting at 12 h post infection. [0215] Table 19. Study design for SEQ ID NO: 17 or SEQ ID NO: 1 efficacy evaluation, P. aeruginosa AR-BANK#0266 extended lung infection model. )
Figure imgf000068_0001
6 SEQ ID NO: 17 + 36 h 10
amikacin
Figure imgf000069_0001
[0216] Groups 1 to 7 are the bacterial enumeration groups. Animals in Group 1 will be sacrificed at 12 h post infection for initial bacterial counts (baseline group) at the time of the first test article dosage. Vehicle and test articles will be intratracheally (IT) administered twice (BID) daily with a 12 h interval (q12h) starting at 12 h post infection. Amikacin will be SC administered at BID q12h. Animals will be sacrificed at 36 h post-infection for bacterial counts. [0217] Groups 8 to 13 are the survival arm study groups. Animals will be monitored for survival until 120 h (5 days) post-infection. Vehicle and test articles will be intratracheally (IT) administered at BID q12h for 5 days starting at 12 h post infection. Amikacin will be SC administered at BID q12h x 5 days. Animals will be monitored for survival. [0218] For control Groups 3 and 8, control reference agent (amikacin 1000 mg/kg) will be subcutaneously (SC) administered twice (BID) daily with a 12 h interval (q12h) starting at 12 h post infection. [0219] Table 20. Dosage information in the SEQ ID NO: 17 or SEQ ID NO: 1 efficacy ev G
Figure imgf000069_0002
Bacterial enumeration groups
1 baseline, 12 h post - - - - s s s s s
Figure imgf000070_0001
am acn 5 mg/kg 10 50 mg/kg 100 mg/kg x 5 days [0220] Table 21. Dosage schedule in the SEQ ID NO: 17 or SEQ ID NO: 1 efficacy evaluation, P. aeruinosa AR-BANK#0266 extended lun infection model stud G
Figure imgf000070_0002
Q : ,
5 Vehicle-DPBS IT, BID q12h
Figure imgf000071_0001
Animal Preparation [0221] The lung infection model with P. aeruginosa strain AR-BANK#0266 will be performed with male specific pathogen-free ICR mice, 5-6 weeks of age, weighing 22 ± 2 g. Animals will be immunosuppressed by two intraperitoneal injections of cyclophosphamide, the first at 150 mg/kg 4 days before infection (Day –4) and the second at 100 mg/kg 1 day before infection (Day –1), prior to infection on Day 0. PDS determined in prior complete blood count studies that this cyclophosphamide treatment schedule resulted in neutropenia (< 100 neutrophils per µL) until Day 2 after infection. [0222] For the 120 h survival arm studies, cyclophosphamide will be administered by four IP injections to render the animals persistently neutropenic over the five-day duration of infection (Gumbo et. al., 2007). The first CP dose, 150 mg/kg, will be administered at four days before infection (Day –4); the second, 100 mg/kg, 24 h before infection (Day –1) prior to infection on day 0, the third, 100 mg/kg on Day +1, and the fourth 100 mg/kg on Day +3. PDS determined in prior complete blood count studies that this cyclophosphamide treatment schedule resulted in i t t t i (< 100 t hil L) til D 4 ft i f ti [0223] All husbandry, caging, waste handling, and animal handling comply with the species- specific recommendations of The Guide for the Care and Use of Laboratory Animals (2011), the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, and follow the PDS internal husbandry SOP (SOP:OPIV04;” Animal Husbandry Management Procedure”). BioLASCO Taiwan will supply all animals for this study. Upon receipt, all animals are quarantined for three days in an SPF facility. Animals that pass quarantine are transferred to appropriate holding rooms for infection studies. [0224] Mice for infection studies are housed in an A-BSL2 vivarium. Cages for mice are 39 × 20 × 16 cm and house up to five animals each. During infection studies, animals are housed in a separate room in negative pressure individually ventilated cages (GM500 IVC seal safe plus cage system; Tecniplast, Italy). All animal rooms are maintained at a temperature range of 20-24°C and humidity between 30-70%, with 12-hour light/dark cycles. These parameters are manually checked twice per day and continuously remotely monitored. Animals have free access to a sterilized standard lab diet [MFG (Oriental Yeast Co., Ltd., Japan)] and autoclaved tap water. Cage-front checks are performed once per day to assure sufficient food and water, dry bedding, normal animal health and behavior and to identify moribund animals. Cages are supplied with sterile aspen chip bedding as well as autoclaved bricks or plastic tunnels for enrichment per our IACUC policy. Cages are changed twice per week and replaced with freshly autoclaved cages, bedding, enrichment, water and food. [0225] Upon receipt, animals will be evaluated with a basic health examination, including appearance, coat, extremities and orifices. Discovery of wounds, hair loss, unkempt appearance, diarrhea or trauma disqualifies the health certification, and disqualified animals will be humanely euthanized according to the “Euthanasia Working Instruction” (SOP: QWCN38). Animals exhibiting signs of illness or abnormal behavior are humanely euthanized immediately to prevent cross-contamination to other animals in the facility. Animal health is observed visually on a daily basis including weekend and holidays. Clinical signs are observed by trained care and research personnel and recorded in the “Clinical Sign Record” (Form: QFIV51) as well as documented in study reports. PDS employs two full-time veterinarians (DVM) who are available 24 hours a day for any animal health issues. [0226] Trained animal care technicians will monitor animals daily throughout all studies to identify animals in pain or distress. PDS SOP “Euthanasia Working Instruction” (From: QWCN38) specifies the criteria for moribund animals and the humane alternatives to experimental endpoints. The criteria include the inability to eat and/or drink, inability to thermoregulate, weight loss (>20%), moribundity, prolonged bleeding, seizures, paralysis, and pain level reaching category E. Animals will be humanely euthanized if any of these criteria are met. [0227] Euthanasia will be performed following the Pharmacology Discovery Services IACUC approved SOP “Euthanasia Working Instruction” (SOP: QWCN38), which follows the 2020 AVMA Guidelines on Euthanasia. Animals will be euthanized using compressed CO2 gas in a CO2 gas chamber. Mice will be placed into the chamber without crowding them. CO2 will be allowed to enter the chamber at a flow rate that will displace at least 20% of the chamber volume per minute. Gas flow will be maintained for at least 1 minute after apparent clinical death. Animals will be verified as dead (lack of respiration, lack of heartbeat) before removal from the chamber. Death will be further confirmed by feeling the chest area for the absence of a heartbeat. [0228] PDS complies with the International Guiding Principles for Biomedical Research (CIOMS) and has an IACUC that operates in accordance with “Regulation for Establishing the Committee of Care and Use of Laboratory Animals”. PDS facility and PDS procedures have been fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) in 2014, 2017 and 2020 (#001553). PDS have a current Foreign Assurance from the Office of Laboratory Animal Welfare (F16-00213, legacy #A5890-01), issued by the PHS/NIH for vertebrate animal studies. [0229] The mouse lung infection model with neutropenic mice is chosen because of the extensive prior work, including publication and acceptance by the scientific community for assessments of antimicrobial efficacy, drug tolerability and pharmacokinetics. Mouse is the lowest reliable and relevant mammalian species to test agents for safety, pharmacokinetics and efficacy. Non-animal models cannot be used for this research because the analysis depends on the interaction of pathogen growth in mammalian tissue and the exposure of the drug to the infection site, which is a feature of distribution and elimination by organ systems. [0230] All animals brought to the PDS facility are assigned to a specific study. All animal use is purposeful and justified, and methods employed are approved by the PDS IACUC. The number of animals used in experiments is based on statistical power analysis (when possible) or on results from similar models and studies. Inoculum Preparation [0231] Our standard protocol for preparing P. aeruginosa cultures for mouse infection studies will be followed. A 0.2 mL aliquot of a single-use glycerol stock (at -80 °C) will be used to seed 20 mL tryptic soy broth (TSB) and then incubated at 35-37 °C with shaking (250 rpm) for 6 h. One mL of the 6-hour culture will be used to seed 99 mL TSB and incubated at 35 – 37⁰C with shaking at 250 rpm for 16 hours. A 20 mL of the 100 mL bacterial culture will be pelleted by centrifugation (3,500 x g) for 15 minutes, then re-suspended in 10 mL cold PBS. [0232] The suspension will be diluted, and the optical density measurements will be used to calculate the CFU count of the suspension and to guide further dilutions to achieve the target inoculum of 3 × 103 CFU/mouse for P. aeruginosa AR-BANK#0266. The PBS suspensions will be stored on ice for no more than one hour prior to animal inoculation. Bacterial count in the challenge organism suspension will be enumerated by dilution plating to suitable plates followed by 20-24 h incubation at 35-37 °C. Challenge [0233] On Day 0, animals will be deeply anesthetized with etomidate-lipuro emulsion (~20 mg/kg, IV). The mouse will be held upright and then drops of bacterial suspension will be gradually released into the nares using a micropipette. A total volume of 20 µL will be administered, 10 µL per nostril. The mouse will be held in an upright position for a couple of minutes until the breath returned to a normal rate and depth. Treatment [0234] The test articles, SEQ ID NO: 17 and SEQ ID NO: 1, will be intratracheally (IT) administered as monotherapy and with amikacin (via SC) combination therapy using the dose schedule, volumes, and concentrations indicated in Table 4 for efficacy. Animals will be deeply anesthetized with isoflurane (3%-5%). The mouse will be held upright, and a 22 G long blunt needle will be directly inserted into the trachea, and then 20 µL of test article solution will be injected directly into the trachea. The mouse will be held in the upright position for about 15 seconds and then placed into the cage for recovery. Animals will be observed at 30 min after dosing to detect acute toxicity which will be recorded and reported, if observed. Animals will be humanely euthanized if severe acute toxicity is observed. Control reference agent, amikacin 1000 mg/kg, will be administered by the route and schedule specified in the Appendix. Post Challenge – efficacy analysis [0235] For bacterial enumeration study arm, lung tissue of infected animal will be aseptically harvested from each of the sacrificed animals, weighed, and homogenized respectively in 1 mL of sterile PBS (pH 7.4) with a Polytron homogenizer. Bacterial burden in the tissue homogenates will be determined by plating 10-fold serial dilutions to MacConkey II agar plates. The CFU per g tissue (CFU/g) will be calculated. Data analysis and statistical analysis – Survival rate and efficacy (120 h groups) [0236] Animals will be monitored for mortality twice daily (AM 9:00/PM 17:00) for 120 h (5 days) after infection. Survival (percentage) of animals will be plotted as a function of time using the Kaplan Meier method using GraphPad Prism. Fisher’s exact test will be used to assess the statistical significance in the survival of the treated animals compared to the vehicle control group at the Day 5 time point. The p value < 0.05 indicates a significant increase in the survival rate of the treated animal group. Data analysis and statistical analysis – Bacterial enumeration and efficacy (36 h groups) [0237] For each animal, the following raw data will be recorded and tabulated: tissue weight and bacterial counts in each tissue homogenate dilution. For each tissue, the homogenate dilution that yielded the largest number of colonies, between 10 to 300 colonies per plate, will be selected to calculate the bacterial counts per gram of tissue (CFU/g). Bacterial counts per gram of tissue (CFU/g) will be tabulated and plotted in GraphPad Prism. The raw colony count data of the homogenate dilutions will be inspected for proportionality within the dilution series. The 10-fold serial dilutions are expected to show 10-fold reductions in counts. Disproportionate data, such as fewer counts in the undiluted homogenate samples compared to the diluted sample, would indicate inhibition of colony growth due to drug carry over from the tissue to the test plate. Aberrant titration data would be reported, if observed. [0238] Data will be plotted in GraphPad Prism as the bacterial counts per gram tissue of control and treatment groups. The difference in bacterial density between the baseline group (12 h initial counts) and the treatment group will be calculated. Significance will be assessed with ANOVA analysis using GraphPad Prism software. [0239] Δ = CFU/g of treatment —CFU/g of baseline [0240] Nonlinear regression will be conducted to estimate the doses that result in bacteriostasis, 1-log10 and 2-log10 reductions in bacterial counts. The dose levels that result in a net static effect, 1-log10 and 2-log10 reductions in counts relative to baseline will be defined. Example 11. Stability Analysis of Compounds per Formulation Formulation appearance, pH, and osmolality results for stability [0241] To more fully understand the stability of peptides corresponding to SEQ ID NO: 1 aerosol forms, multiple types of analysis of SEQ ID NO: 1 formulations have been performed. These tests have assessed the stability and physical properties of SEQ ID NO: 1 aerosol formulations over time, across a temperature and humidity range, and in combination with different excipients. Additionally, experiments have been performed to assess the appearance and aggregation of SEQ ID NO: 1 formulated with different excipients [0242] Aerosol formulations of SEQ ID NO: 1 were prepared via combining test peptides disclosed herein with 50 mL of 0.9 % w/v saline buffer or 0.05 M pH 5 acetate buffer, adjusting pH of the resulting solution to pH of 5 via addition of 1N acetic acid or sodium hydroxide, and adjusting osmolality via addition of sodium chloride to 300 mOsm/kg. In the case of Formulations 3-12, adding acetate buffer was used, whereas control Formulations 1 and 2 used saline buffer. The excipients tested include 1 % (w/w) D-mannitol, 1 % (w/w) D-trehalose, 0.05 % (w/w) Polysorbate 80 (PS 80), and 0.5 % (w/w) Human serum albumin (rh-HSA). [0243] Table 22 shows the appearance, pH, and osmolality experimental results according to SEQ ID NO: 1 in different formulations with different excipients. Included in the table is the initial pH, appearance, and osmolality of SEQ ID NO: 1 Formulations 1-12, as well as data for pH, appearance, and osmolality under two physical conditions; one experiment at 5o C and the other at 40o C and 75 % relative humidity. The pH, appearance, and stability were measured after one month and after three months under both conditions. SEQ ID NO: 1 was tested at concentrations of 1 mg/mL and 10 mg/mL. [0244] The formulations of SEQ ID NO: 1 aerosol with the excipients tested showed neither higher temperature nor higher SEQ ID NO: 1 concentration significantly affected the pH of the formulations tested aside from the Polysorbate 80 (PS80) excipient. Osmolality and pH were consistent across the 3 month period for all SEQ ID NO: 1 formulations tested. This shows the stability of the particular aerosol formulations over time. [0245] Table 23 shows the aggregation data for the SEQ ID NO: 1 formulations. The analysis was done upon sample preparation, at 1 month, and at 3 months as well as data for storage at 5o C and at 40o C and 75 % relative humidity via size exclusion chromatography (SEC). When test article SEQ ID NO: 1 was examined with a variety of excipients, the formulations did not form aggregates under conditions tested and demonstrated a clear, colorless appearance. Neither higher temperature nor higher SEQ ID NO: 1 concentration significantly affected the aggregation of particles. [0246] Table 22. Appearance, pH, and osmolality results of SEQ ID NO: 1 aerosol formulations. , T , H F C F C
Figure imgf000076_0001
Formulation, visible visible visible 100 mg/mL particulates particulates particulates
Formulation 3, Clear, Clear, Clear, 0 colorless and colorless and colorless and F 0 F F F F F F F r F r
Figure imgf000077_0001
. g p p p [0247] Table 23. Size Exclusion Chromatography (SEC) Results for Stability of different formulations of SEQ ID NO: 1. ,
Figure imgf000077_0002
F lti 7 Dt hl (1% / ) F lti N Ob d N Ob d N Ob d 1.0 mg/mL
Figure imgf000078_0001
Decomposition of SEQ ID NO: 1 under assay conditions [0248] In order to analyze possible decomposition of SEQ ID NO: 1 aerosol formulations, LC- MS analysis was performed on samples of SEQ ID NO: 1 aerosol formulations with excipients under different physical conditions. One experiment was done at 5o C and the other at 40o C and 75 % relative humidity. The analysis was done upon samples preparation, after one month, and after three months under both physical conditions for Formulations 1-12. Table 24 shows the LC-MS results for the control formulations without excipient. There is virtually no decomposition of SEQ ID NO: 1 within this aerosol formulation over time or at higher temperature and humidity. [0249] Table 25 shows the results of Formulation 3 and Formulation 4, which have 0.05M acetate as the buffer. Acetate did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity. This shows 0.05M acetate is a viable excipient to store SEQ ID NO: 1 in aerosol form over time. [0250] Table 26 shows the results of Formulation 5 and Formulation 6, which have 1% (w/w) D-mannitol as the excipient. D-mannitol did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity. This shows 1% (w/w) D- mannitol is a viable excipient to administer SEQ ID NO: 1 in aerosol form. [0251] Table 27 shows the results of Formulation 7 and Formulation 8, which have 1% (w/w) D-trehalose as the excipient. D-trehalose did not significantly increase aerosol SEQ ID NO: 1 decomposition over time or at elevated temperature and humidity. This shows 1% (w/w) D- trehalose is a viable excipient to administer SEQ ID NO: 1 in aerosol form. [0252] Table 28 shows the results of Formulation 9 and Formulation 10, which have 0.05% (w/w) polysorbate 80 (PS80) as the excipient. PS80 significantly increased decomposition of 1.0 mg/mL aerosol SEQ ID NO: 1 at elevated temperature and humidity. This shows that SEQ ID NO: 1 has unpredictable stability when formulated as an aerosol with 0.05 % (w/w) PS80. [0253] Table 29 shows the results of Formulation 11 and Formulation 12, which have 0.5 % (w/w) rh-HSA as the excipient. rh-HSA had slightly higher decomposition product percentage by LC-MS (3.6 percent impurities) than other excipients (<2.9 % impurities) at 1.0 mg/mL SEQ ID NO: 1 concentration and elevated temperature and humidity conditions. [0254] Table 24. Assay and Related Substances Results for Stability for Formulation 1 and Formulation 2 (Average of 2 injections). Formulation Assay (% LC) % Impurity (RRT) , C , C
Figure imgf000079_0001
[0255] Table 25. Assay and Related Substances Results for Stability Formulation 3 and Formulation 4 (Average of 2 injections). , ,
Figure imgf000079_0002
100 mg/mL 02 (097) 0.2 (0.98) 0.2 (0.98) 0.2 (0.98) [02
Figure imgf000080_0001
56] Table 26. Assay and Related Substances Results for Stability Formulation 5 and Formulation 6 (Average of 2 injections). Formulation Assay (% LC) % Impurity (RRT) , F w , F w
Figure imgf000080_0002
[0257] Table 27. Assay and Related Substances Results for Stability Formulation 7 and Formulation 8 (Average of 2 injections). , F w
Figure imgf000080_0003
Total Imp. 2.4 2.4 2.7 T=0 T=1M 5 o T=1M 40 o C, o T=1M 40 o C, C 75%RH T=0 T=1M 5 C 75%RH F w
Figure imgf000081_0001
[0258] Table 28. Assay and Related Substances Results for Stability Formulation 9 and Formulation 10 (Average of 2 injections). F l i A % LC % I it RRT , m , F
Figure imgf000081_0002
08 (102) 09 (102) 09 (102) 0.2 (1.03) 0.2 (1.03) 0.2 (1.03) [02
Figure imgf000082_0001
] a e . ssay an e a e u s ances esu s or a y ormu a on an Formulation 12 (Average of 2 injections). Formulation Assay (% LC) % Impurity (RRT) 1.0 m ,
Figure imgf000082_0002
Example 12. In vitro lung tissue toxicity models Experimental background [0260] In order to assess respiratory toxicity of aerosol distribution of the peptides SEQ ID NO:1 and SEQ ID NO: 17, several assays and tests were performed using cellular lung tissue models. In particular, the MucilAirTM in vitro lung tissue system was used for testing of several possible forms of cytotoxicity. The MucilAirTM in vitro tissue model is a functional model of human airway epithelium, is derived from cells collected from the airways of healthy donors and cultured at the air liquid interface, exhibiting a pseudostratified, ciliated epithelium which secretes mucus. Manipulations of the MucilAirTM cells were performed in Class II biological containment hoods using sterile reagents and consumables. All incubations of cells were performed in humidified incubators set to maintain a temperature of 37°C with a 5% CO2 atmosphere (standard conditions) Trans-epithelial electrical resistance (TEER) of the tissue was measured 3 days prior to dose application using a Millipore Millicell® ERS-2 meter with chopstick electrodes. Following TEER measurement, the apical liquid was aspirated and discarded, and the tissues tapped gently on absorbent paper to dry. Positive control response was calibrated with Sodium dodecyl sulfate, and negative control was measured with phosphate buffered saline (PBS), and a third Lysis solution was used as a lactate dehydrogenase (LDH) release benchmark. Trans-epithelial Electrical Resistance (TEER). Test samples were prepared in either pH 7.4 PBS buffer (280-330 mOsm/kg) or water and tested at multiple concentrations including 10 mg/mL, 1 mg/mL, 0.1 mg/mL, 10 μg/mL, 1 ug/mL, 100 ng/mL. [0261] Following TEER, tissues were transferred to fresh pre-warmed media and a final media change was done immediately prior to dosing. Tissues were dosed with each concentration of test sample and controls as follows, and then returned to an incubator in standard conditions for exposure. Doses were applied to tissues by pipetting directly into the center of the apical surface. At the end of the exposure period, the dose on the apical surface of tissues was pooled with basal media and tissue rinsed three times with pre-warmed saline (ca 0.5 mL per rinse). TEER was thereafter measured again, as described for pre-dose. Spent culture media (pooled with any liquid collected from the apical chamber) was retained for the LDH assay, following TEER, tested tissues underwent an ATP content assay. In the main cytotoxicity test, 2 MucilAir™ tissues per treatment were exposed to 6 concentrations of each test item within a dose volume of 30 µL, for 24 hours. Doses were applied to tissues by pipetting directly into the center of the apical surface of the cells, taking care not to contact the surface with the pipette tip. TEER was measured prior to dosing. TEER, Lactate Dehydroenase (LDH) release and ATP content were measured at 24 hours post dose. Appropriate controls were tested in parallel (n = 2). [0262] The release of LDH from cells was measured using the CytoTox ONE™ Homogeneous Membrane Integrity Assay kit according to the manufacturer’s instructions (Promega, 2009). This assay was performed on the day of media collection. Cytotoxicity was assessed at 24 h, and compared to the benchmark LDH release controls. Duplicate aliquots (100 μL) of culture supernatant (pooled with any liquid that has permeated into the apical compartment) were collected from each well and transferred to black walled 96 well plates. Individual vials of CytoTox-ONE™ Substrate Mix were reconstituted in Assay Buffer (11 mL each), according to the manufacturer’s instructions. The collected culture supernatants will be allowed to reach ambient temperature before adding reconstituted Substrate Mix (100 μL) to each well. The reaction was allowed to proceed (protected from light with foil) at ambient temperature for 10 min and was stopped by adding Stop Solution (50 μL) to each well. Fluorescence of wells was read at 590 nm with excitation at 544 nm (544ex/590em) within 2 h of stopping the reaction. [0263] The metabolic competence of cells was further assessed by measuring cellular ATP content. ATP content was assessed using the CellTiter-Glo® Luminescent Cell Viability Assay, according to the manufacturer’s instructions (Promega, 2015). Following reconstitution of the assay reagents, tissues were transferred to empty 24-well plates and assay reagent (200 μL) was added apically to each tissue. Plates were shaken for ca 10 min and then incubated for >25 min at room temperature, protected from light. Following incubation, duplicate aliquots of lysate (50 μL) from each tissue were transferred to white 96-well plates. Luminescence of wells were read using a luminometer following incubation. Blank assay reagent was also analyzed to account for background luminescence. The ATP results are shown Figure 5 and in Table 30. [0264] Table 30 shows TEER values, LDH release percentage, and average ATP content for cells exposed to SEQ ID NO: 1 and SEQ ID NO: 17. The highest doses of both SEQ ID NO: 1 and SEQ ID NO: 17 (10 mg/mL) demonstrated a significant reduction in electrical resistance of cells 24 hours post-dose. TEER data for both peptides at 100 ng/mL –0.1 mg/mL were comparable to that of the vehicle and untreated (Air Liquid Interface) controls. This indicates that the peptide treatments have no impact on cellular tight junction integrity. An initial stress response (an increase in TEER followed by a sharp decrease) was observed with both peptides at 1 –10 mg/mL. Mean TEER values following experimental procedures are visualized in Figure 3. Mean LDH release percentage results are shown in Figure 4, which shows that LDH release of different formulations at concentrations from 100 ng/ml to 1 mg/ml is comparable to that of the vehicle and untreated (Air Liquid Interface) controls. Mean ATP content results shown in Figure 5, which shows that ATP release of different formulations at concentrations from 100 ng/ml to 1 mg/ml is comparable to that of the vehicle and untreated (Air Liquid Interface) controls. [0265] The LDH release experiments and average ATP content experiments in Table 30 also demonstrate that, at concentrations between 100 ng/mL –1 mg/mL, cytotoxicity results were comparable to that of the vehicle and untreated (Air Liquid Interface) controls. The positive control, SDS, demonstrated much larger LDH release percentage than test items, as well as much lower ATP content than peptide concentrations between 100 ng/mL –1 mg/mL. Overall, the peptides were found to be non-cytotoxic in the TEER, LDH release percentage, and average ATP concentration experiments at lower concentrations. [0266] Table 30. Cytotoxicity parameter assay results from MucilAir tissues exposed to test ite T n
Figure imgf000084_0001
(%) Vehicle Control (pH 611 0.08 100.00 7 P ( A S n S µ S µ S m S m S m S n S µ S µ S m S m S m
Figure imgf000085_0001
g [0267] Following review of the main cytotoxicity data, 3 selected concentrations of each test item were applied to a further 2 tissues, for Mucociliary Clearance (MCC) and Cilia Beat Frequency (CBF) analysis. Based on the results of the prior assays, 3 concentrations of each test item were selected for Cilia Beating Frequency (CBF) and Mucociliary Clearance (MCC) analysis (after 24 h treatment, n=2). A vehicle group and untreated ALI group were also measurement. Following exposure, CBF was assessed. Images of each tissue were captured at a rate of 125 frames per second (fps) at 5x or 10x magnification using a Leica DMi8 microscope with a Hamamatsu high speed digital camera. The focus was adjusted just above the cell layer to capture the cilia at their most active point. Polystyrene microbeads were diluted to ca 1:4 or more. Figure 7 shows the effect of SEQ ID NO: 1, SEQ ID NO:17, and controls on the percent of active cilia within the CBF experiment. Figure 8 shows the effect of treatment of test items on CBF frequency of tissue. Examples of CBF images among test samples are shown in Figure 9, Figure 10, and Figure 11. [0268] The % Active and CBF results are tabulated in Table 31. The results show that the lower concentrations of SEQ ID NO: 1 or SEQ ID NO: 17 treatment show comparable results of ciliary health relative to controls. [0269] Table 31. CBF results comparing vehicle, control, and treatment from MucilAir tissues exposed to test items or control treatments. T e V A S S S S S S
Figure imgf000086_0001
[0270] Immediately following CBF assessment, the MCC experiments were performed. Diluted polystyrene microbeads (10-30 μL) were applied to cellular tissues and multiple consecutive videos (up to 10s) and images of the microbeads on top of the cilia were captured. If possible, different areas of the tissue were captured in each video. Snapshots of the imaging results are shown in Figure 12 (Vehicle test) and Figure 13 (1 mg/mL treatment). Quantitative results are shown Figure 6 and in Table 32. Taken together, functional in vitro changes (MCC, cilia viability, CBF) are decreased at the highest concentration tested in the dose range of 0.1 - 1.0 mg/mL, and at concentrations lower than cytotoxic (10 mg/mL) concentrations. [0271] Table 32. MCC Analysis from MucilAir tissues exposed to test items or control tre
Figure imgf000086_0002
Treatment Mean MCC of both replicates (%)
Figure imgf000087_0001
Example 13: In vitro bacterial lung infection model
[0272] MucilAir™ tissues were inoculated with Pseudomonas aeruginosa to model lung infections and observe the effect of SEQ ID NO: 1 and SEQ ID NO: 17 on the colony forming units (CFU) measured in the cellular tissue In the study, 4 MucilAir™ tissues per treatment were exposed to 3 concentrations of each test item in pH 7.4 PBS buffer for 24 h. Appropriate controls were tested in parallel (n = 4). TEER was measured prior to dosing to compare upon inoculation with bacteria. CFU analysis was performed after 24 h of exposure. The results of the TEER measurements are shown in Figure 14 and demonstrate that the lower concentrations of both SEQ ID NO: 1 and SEQ ID NO: 17 resulted in an electrical resistance parameter similar to vehicle controls.
[0273] Figure 15 and Figure 16 show Pseudomonas aeruginosa CFU data observed across treatment regimens following infection. Figure 15 shows that treatment with higher concentration of SEQ ID NO: 1 significantly (p < 0.05) reduced the number of bacteria in apical rinse samples and that the positive control, the antibiotic Tobramycin, was very effective in reducing CFU. Given that the antibiotic control tobramycin has high cytotoxicity in vivo, this might provide a distinct advantage to treatment with SEQ ID NO: 1. Figure 16 shows a one-way ANOVA of vehicle control vs both test item, confirming the ability of the 0.8 mg/mL SEQ ID NO: 1 treatment to reduce bacterial CFU.
Example 14: In vitro growth assay of pathogenic bacteria in the presence of SEQ ID NO: 1 and SEQ ID NO: 17
[0274] Bacterial growth from CF patient isolates was measured in the presence of SEQ ID NO: 1 and SEQ ID NO: 17. Strains were selected from the collection of the Burkholderia cepacia Research Laboratory and Repository (BcRLR) at the University of Michigan. The strain set was enriched for isolates that were recovered from CF respiratory specimens within the last five years, are genotypically distinct, and are from diverse geographical locations in the US to avoid duplicate testing of the same strain. In addition, the set was enriched for isolates previously tested for susceptibility against a custom antibiotic plate (TREK Lab Services) that included ceftazidime, ceftazidime /avibactam, ceftolozane /tazobactam, meropenem, meropenem /vaborbactam, aztreonam, colistin, minocycline, ciprofloxacin, levofloxacin, moxifloxacin, piperacillin /tazobactam, imipenem, and tigecycline. [0275] Minimal inhibitory concentrations (MICs) were determined using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute (CLSI M07-A10). Peptides were serially diluted in 96 well plates (range 32 µg/ml – 250 ng/ml) in cation adjusted Mueller Hinton media (pH 7.0) or RPMI-1640 media (pH 7.0) supplemented with a final concentration of 0.165 mol/l MOPS, 0.002% Tween 80, and plates were inoculated with 105 CFU bacteria from overnight growth. Regent controls included wells with bacteria alone (no peptide) and media alone (no bacteria or peptide). Control strains included P. aeruginosa ATCC 27853, E. coli ATCC 25922, and S. aureus ATCC 29213. Strains and controls were tested in triplicate and incubated overnight at 37oC without shaking. MICs were determined using both standard visualization and spectrophotometric optical density. MICs were assigned as the lowest concentration of peptide that decreases OD by 80% relative to non-peptide controls. S. aureus strains were similarly tested against clindamycin (range 4 µg/ml – 30 ng/ml), daptomycin (range 4 µg/ml – 30 ng/ml) supplemented to 50 µg/ml of calcium, linezolid (range 16 µg/ml – 120 ng/ml), trimethoprim /sulfamethoxazole [1:19] (range 16/304 µg/ml – 125/2375 ng/ml), and vancomycin (range 16 µg/ml – 120 ng/ml). The results are shown in Table 33. [0276] Table 33. MIC values for SEQ ID NO: 1 and SEQ ID NO: 17 during in vitro testing with CF clinical isolates. S B B B B S S S S
Figure imgf000088_0001
RPMI SEQ ID NO: 17 2 2 [0277] These in vitro results suggest that SEQ ID NO: 1 and SEQ ID NO: 17 are effective in general and most effective against S. maltophilia and S. aureus under the conditions tested. [0278] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the present disclosure may be employed in practicing the present disclosure. It is intended that the following claims define the scope of the present disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS What is claimed is: 1. A method for preventing or treating a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: a. a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg- Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg (SEQ ID NO: 23); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient; wherein the pharmaceutical composition comprises a pH value of at least about 4.5 to at least about 6.5.
2. The method of claim 1, wherein said administering comprises an oral administration, an oronasal administration, an intra-nasal administration, an intra-trachael administration, an inhalatory administration, an intravenous administration, or any combination thereof.
3. A method for treating or preventing a lung disease or injury in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises: a. a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg- Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg (SEQ ID NO: 23); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation.
4. A method comprising administering a therapeutically effective amount of a pharmaceutical composition to asubject, wherein the subject has or is at risk of having an acute or chronic lung infection caused by cystic fibrosis (CF), wherein the pharmaceutical composition comprises: a. a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg- Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg (SEQ ID NO: 23); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation.
5. The method of any one of claims 1-4, wherein the pharmaceutical composition comprises an aerosolized composition.
6. The method of any of claims 1-3 or 5, wherein the lung disease or injury is pneumonia.
7. The method of any of claims 1-3 or 5, wherein the lung disease or injury is acute or chronic lung infection.
8. The method of any of claims 1-7, wherein the pharmaceutical composition comprises a dry powder formulation.
9. The method of any of claims 1-8, wherein the administering further comprises using a nebulizer, a pressurized metered-dose inhaler (MDI), a mechanical ventilator, a dry powder inhaler (DPI), a soft mist inhaler, or a concentrated aerosol generator.
10. The method of claim 9, wherein the nebulizer is a jet nebulizer, an ultrasonic nebulizer, or a vibrating mesh nebulizer.
11. The method of claim 10, wherein the nebulizer is a vibrating mesh nebulizer.
12. The method of claim 10, wherein the DPI is a single-dose DPI or a multi-dose DPI.
13. The method of claim 10, wherein the DPI is a reusable DPI or a nonresuable DPI.
14. The method of any of claims 1-13, wherein the pharmaceutical composition is a liquid composition.
15. The method of any of claims 1-14, wherein the pharmaceutical composition is administered to a pulmonary system.
16. The method of claim 7, wherein the acute or chronic lung infection is hospital acquired pneumonia.
17. The method of claim 16, wherein the hospital acquired pneumonia is ventilator acquired pneumonia.
18. The method of claim 7, wherein the acute or chronic lung infection is a bacterial pneumonia.
19. The method of claim 18, wherein the bacterial pneumonia is caused by a bacteria selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, methicillin- resistant Staphylococcus epidermidis, Staphylococcus lugdensis, methicillin-resistant Staphylococcus lugdensis, Staphylococcus haemolyticus, Staphylococcus spp., Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warnerii, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus pettenkoferi, Klebsiella pnuemoniae, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Streptococcus pneumoniae, Enterobacter species, Cintrobacter species, Stenotrophomonas maltophilia, Acinetobacter species, Burkholderia cepacia, methicillin-resistent Staphylococcus aureus (MRSA), Haemophilus influenzae, Burkholderia multivorans, Burkholderia gladioli, Achromobacter xylosoxidans, Achromobacter dolens, Achromobacter ruhlandii, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus constellatus, Enterococcus faecalis , Enterococcus faecalis - vancomycin-susceptible, Enterococcus faecium, Enterococcus faecium - vancomycin-susceptible Corynebacterium jeikeium Lactobacillus acidophilus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Acinetobacter baumannii, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter haemolyticus, Acinetobacter radioresistens, Enterobacter cloacae, Enterobacter aerogenes, Stenotrophomonas maltophilia, Citrobacter freundii, Citrobacter koseri, Citrobacter sedlakii, Citrobacter braakii, Morganella morganii, Providencia rettgeri, Providencia stuartii, Salmonella typhimurium, Shigella dysenteriae, Moraxella catarrhalis, Neisseria gonorrhoeae, Propionibacterium acnes, Clostridioides difficile, Clostridioides perfringens, Bacteroides fragilis, Prevotella bivia, Eggerthella lenta, Peptostreptococcus anaerobius and any combination thereof.
20. The method of claim 6, wherein the pneumonia is a viral pneumonia.
21. The method of claim 20, wherein the viral pneumonia is caused by a virus selected from the group consisting of influenza, respiratory syncytial, cytomegalovirus, and any combination thereof.
22. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Arg- Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg- Arg (SEQ ID NO: 1).
23. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Arg- Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg- Arg (SEQ ID NO: 1).
24. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 1.
25. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises at least about 95% sequence identity to the polypeptide sequence Arg-Trp- Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17).
26. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises at least about 99% sequence identity to the polypeptide sequence Arg-Trp- Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17).
27. The method of any of claims 1-21, wherein the peptide or pharmaceutical acceptable salt thereof comprises SEQ ID NO: 17.
28. The method of any one of claims 1-27, wherein the pharmaceutical composition comprises a osmolality value that is at least about 270 mOsm/kg to at least about 350 mOsm/kg.
29. The method of any one of claims 1-27, wherein the the pharmaceutical composition comprises an osmolality value that is at least about 280 mOsm/kg
30. The method of any one of claims 1-27, wherein the pharmaceutical composition comprises an osmolality value that is at least about 300 mOsm/kg.
31. The method of any one of claims 1-27, wherein the pharmaceutical composition comprises an osmolality value that is at least about 310 mOsm/kg.
32. The method of any one of claims 1-27, wherein the pharmaceutical composition comprises an osmolality value that is at least about 280 mOsm/kg and 350 mOsm/kg.
33. The method of any one of claims 1-32, wherein the pharmaceutical composition comprises acetate.
34. The method of any one of claims 1-32, wherein the pharmaceutical composition comprises mannitol.
35. The method of any one of claims 1-32, wherein the pharmaceutical composition comprises trehalose.
36. The method of any one of claims 1-32, wherein the pharmaceutical composition comprises rh-HSA.
37. The method of any one of claims 1-32, wherein the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose.
38. The method of any one of claims 1-37, wherein the pH value is at least about 4.5 to at least about 5.5.
39. The method of any one of claims 1-37, wherein the pH value is at least about 5.0 to at least about 5.5.
40. The method of any one of claims 1-37, wherein the pH value is at least about 5.0.
41. The method of any one of claims 1-37, wherein the pH value is at least about 4.5 to at least about 6.0.
42. The method of any one of claims 1-38, wherein the pH value is at least about 5.5.
43. The method of any of claims 1-42, further comprising administering a neutrophil elastase.
44. The method of claim 43, wherein the neutrophil elastase is human neutrophil elastase.
45. The method of any of claims 1-44, further comprising administering a lung surfactant.
46. The method of claim 45, wherein the lung surfactant comprises about 25 mg/mL phospholipids, about 0.5-1.75 mg/mL triglycerides, about 1.4-3.5 mg/mL free fatty acids, and about 1.0 mg/mL protein.
47. The method of any of claims 1-46, further comprising inhibiting an inflammatory response.
48. The method of claim 47, wherein the inflammatory response is quantified by measuring an expression level of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6).
49. The method of any one of claims 1-48, wherein said peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.01 µg/mL to at least about 10 mg/mL.
50. The method of any one of claims 1-49, wherein said peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.1 mg/mL to at least about 5 mg/mL.
51. The method of any one of claims 1-49, wherein said peptide or pharmaceutically acceptable salt thereof is administered at a concentration from at least about 0.5 mg/mL to at least about 1 mg/mL.
52. The method of any one of claims 1-49, wherein said peptide or pharmaceutically acceptable salt thereof is present at a concentration of at least about 1 mg/mL.
53. The method of any one of claims 1-49, wherein said peptide or pharmaceutically acceptable salt thereof is present at a concentration from least about 0.5 mg/mL to at least about 15 mg/mL.
54. The method of claim 53, wherein said peptide or pharmaceutically acceptable salt thereof is present at a concentration of at least about 1 mg/mL.
55. The method of claim 54, wherein said peptide or pharmaceutically acceptable salt thereof is present at a concentration at least about 10 mg/mL.
56. The method of any one of claims 1-55, wherein the excipient is a salt.
57. The method of claim 56 wherein the salt is selected from the group consisting of sodium, bicarbonate, sodium chloride, sodium lactate, potassium chloride, calcium chloride, magnesium chloride, and any combination thereof.
58. The method of any one of claims 1-57, wherein the pharmaceutical composition further comprises a pH buffering agent.
59. The method of claim 58 wherein the pH buffering agent is selected from the group consisting of (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), sodium hydrogen phosphate, sodium phosphate, magnesium phosphate, potassium dihydrogenphosphate, sodium bicarbonate, tris(hydroxymethyl)aminomethane, sodium citrate, and any combination thereof.
60. The method of any one of claims 1-59, wherein the pharmaceutical composition further comprises a pH adjusting agent.
61. The method of claim 60 wherein the pH adjusting agent is hydrochloric acid, sodium hydroxide, ammonium hydroxide, or any combination thereof.
62. The method of any one of claims 1-61, wherein the excipient is a sugar.
63. The method of any one of claims 1-62, wherein the pharmaceutical composition further comprises a second antibiotic.
64. The method of claim 63, wherein the second antibiotic is selected from the group consisting of piperacillin, tazobactam, cefepime, ceftazidime, ciprofloxacin, levofloxacin, amikacin, gentamicin, tobramycin, imipenem, meropenem, linesolid, vancomycin, and any combination thereof.
65. The method of any one of claims 1-64, wherein the pharmaceutical composition further comprises a propellant.
66. The method of claim 65, wherein the propellant is 1,1,1,2-tetrafluoroethane or 1,1,- difluoroethane.
67. The method of any one of claims 1-66, wherein the pharmaceutical composition is administered to the subject at least once per day.
68. The method of any one of claims 1-67, wherein the pharmaceutical composition is administered to the subject at least twice per day.
69. The method of any one of claims 1-68, wherein the treating or preventing lasts over a course of at least about 1 day to at least about 10 years.
70. The method of claim 69, wherein the course is at least about 12 months.
71. The method of claim 69, wherein the course is at least about 2 months.
72. The method of claim 69, wherein the course is at least about 1 months.
73. The method of claim 69, wherein the course is at least about 2 weeks.
74. The method of any one of claims 1-73, wherein the pharmaceutical composition is in form of a unit dose.
75. A kit, comprising the pharmaceutical composition or the unit dose of any one of claims 1-74 and instructions for use of the pharmaceutical composition for treating or preventing pneumonia and a nebulizer.
76. The kit of claim 75, wherein the nebulizer is a vibrating mesh nebulizer.
77. The kit of claim 75 or 76, wherein the pharmaceutical composition is a dry powder.
78. The kit of claim 75 or 76, wherein the pharmaceutical composition is a liquid.
79. The kit of claim 75 or 76, wherein the pharmaceutical composition is an aerosol.
80. The kit of any of claims 75-79, wherein the pharmaceutical composition has a pH between 4.5 and 6.5.
81. An inhaler kit, comprising the pharmaceutical compositions in any one of claims 1-80 in an inhaler and instructions for use of the pharmaceutical composition for preventing or treating lung disease or infection.
82. The inhaler kit of claim 81, wherein the pharmaceutical composition is a dry powder.
83. The inhaler kit of claim 81, wherein the pharmaceutical composition is a liquid.
84 The inhaler kit of claim 81 wherein the pharmaceutical composition is an aerosol
85. The inhaler kit of any one of claims 81-84, wherein the pharmaceutical composition has a pH between 4.5 and 6.5.
86. An inhalable pharmaceutical composition comprising: a. a peptide or pharmaceutically acceptable salt thereof comprising at least about 70% sequence identity to a polypeptide sequence of: Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 15); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 16); Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 17); Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Arg (SEQ ID NO: 18); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg (SEQ ID NO: 19); Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Trp-Val-Arg-Arg (SEQ ID NO: 1); Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Trp-Arg-Trp-Trp-Arg-Arg- Trp-Trp-Arg-Arg (SEQ ID NO: 20); Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg- Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 21); Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg- Arg-Val-Trp-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg (SEQ ID NO: 22); Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg- Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val- Arg-Arg (SEQ ID NO: 23); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Arg-Arg-Val-Val-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Val-Val-Arg-Arg (SEQ ID NO: 24); Arg-Val-Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val- Val-Arg-Val-Val-Arg-Arg-Trp-Val-Arg-Arg-Val-Arg-Arg-Val-Trp-Arg-Arg-Val-Val-Arg- Val-Val-Arg-Arg-Trp-Arg-Val-Val (SEQ ID NO: 25); or any combination thereof; and (b) at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is an inhalation formulation, and (c) wherein the pharmaceutical composition comprises a pH value of at least about 4.5 to at least about 6.5.
87. The composition of claim 86, wherein the pharmaceutical composition is a dry powder.
88 The composition of claim 86 wherein the pharmaceutical composition is a liquid
89. The composition of claim 86, wherein the pharmaceutical composition is an aerosol.
90. The composition of any one of claims 86-89, wherein the pharmaceutical composition comprises an osmolality value that is between 270 mOsm/kg and 350 mOsm/kg.
91. The composition of any one of claims 86-90, wherein the pharmaceutical composition comprises acetate.
92. The composition of any one of claims 86-90, wherein the pharmaceutical composition comprises mannitol.
93. The composition of any one of claims 86-90, wherein the pharmaceutical composition comprises trehalose.
94. The composition of any one of claims 86-90, wherein the pharmaceutical composition comprises rh-HSA.
95. The composition of any one of claims 86-90, wherein the pharmaceutical composition comprises saccharin, sorbitol, sucrose, povidone, crospovidone, or hydroxypropyl methylcellulose.
96. The composition of any one of claims 86-95, wherein the pharmaceutical composition further comprises a neutrophil elastase.
97. The composition of claim 96, wherein the neutrophil elastase is human neutrophil elastase.
PCT/US2022/076667 2021-09-17 2022-09-19 Treatment of lung disease or injury using engineered antimicrobial peptides WO2023044487A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030036627A1 (en) * 2001-02-16 2003-02-20 Montelaro Ronald C. Virus derived antimicrobial peptides
US20100204154A1 (en) * 2007-09-11 2010-08-12 Dorian Bevec Use of the peptide rfmwmr as a therapeutic agent
US20180371059A1 (en) * 2017-03-03 2018-12-27 Massachusetts Institute Of Technology Antimicrobial constructs and uses thereof
WO2019089657A1 (en) * 2017-10-30 2019-05-09 Allvivo Vascular, Inc. Delivery systems for administration of cationic biological actives
US20200071361A1 (en) * 2017-03-03 2020-03-05 Peptilogics, Inc. Engineered antimicrobial amphiphilic peptides and methods of use

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030036627A1 (en) * 2001-02-16 2003-02-20 Montelaro Ronald C. Virus derived antimicrobial peptides
US20100204154A1 (en) * 2007-09-11 2010-08-12 Dorian Bevec Use of the peptide rfmwmr as a therapeutic agent
US20180371059A1 (en) * 2017-03-03 2018-12-27 Massachusetts Institute Of Technology Antimicrobial constructs and uses thereof
US20200071361A1 (en) * 2017-03-03 2020-03-05 Peptilogics, Inc. Engineered antimicrobial amphiphilic peptides and methods of use
WO2019089657A1 (en) * 2017-10-30 2019-05-09 Allvivo Vascular, Inc. Delivery systems for administration of cationic biological actives

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