KR101769666B1 - Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof - Google Patents
Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof Download PDFInfo
- Publication number
- KR101769666B1 KR101769666B1 KR1020150051734A KR20150051734A KR101769666B1 KR 101769666 B1 KR101769666 B1 KR 101769666B1 KR 1020150051734 A KR1020150051734 A KR 1020150051734A KR 20150051734 A KR20150051734 A KR 20150051734A KR 101769666 B1 KR101769666 B1 KR 101769666B1
- Authority
- KR
- South Korea
- Prior art keywords
- irinotecan
- doxorubicin
- weight
- cancer
- present
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Abstract
The present invention relates to a composition comprising 10 to 70 parts by weight of doxorubicin and 10 to 70 parts by weight of irinotecan added to 100 parts by weight of a polyethylene glycol-block-polyaspartic acid copolymer. And a biodegradable lipid coated with the mixture. The pharmaceutical composition has pH-dependent release and sustained-release properties, and is useful as a topoisomerase I type (Topoisomerase-1) and type 2 (topoisomerase-2), as well as maximizing the efficacy of anticancer drugs in the treatment of cancer-resistant cancer cells.
Description
The present invention relates to a ratiometric nanomedicine capable of delivering two drugs simultaneously to a tumor site by controlling the concentration and ratio of the two drugs.
Cancer is one of the most deadly diseases worldwide and is one of the deadliest threats to human health. In the United States alone, there are approximately 1.3 million new cancer patients each year, the second leading cause of death after cardiovascular disease, and approximately one out of four deaths is estimated to be cancer. Most of these deaths are due to solid cancers. Although there has been considerable progress in the medical treatment of certain cancers, the overall 5-year survival rate for all cancers has improved by only about 10% over the past 20 years.
Cancer, or malignant tumors rapidly metastasize and grow in an uncontrolled manner, it is extremely difficult to detect and treat them on time.
Currently, surgery, radiation therapy, and chemotherapy are used to treat cancer. Among them, chemotherapy is a method of treating cancer using an anticancer drug, and was used in earnest by obtaining a cure effect by using methotrexate for choriocarcinoma. Today, about 60 kinds of various anticancer drugs are used. Recently, as knowledge of cancer development and characteristics of cancer cells is well known, researches on the development of new anticancer drugs are being actively carried out.
Most of the anticancer drugs currently being used for chemotherapy are chemotherapy drugs.
However, due to the low treatment rate of chemotherapeutic agents and problems such as multi-drug resistance (MDR), combined chemotherapy with two or more anticancer drugs has received attention in most chemotherapy regimens. Concomitant chemotherapy is synergistic in vitro, as it is empirically designed based on the maximal tolerated dose of the two anticancer drugs (the maximum dose that does not cause a drug-induced hazard).
However, in actual practice, the synergistic effect is markedly reduced, and there is also the risk of serious side effects such as immunosuppression through combined chemotherapy or cardiac toxicity.
Therefore, the development of ratiometric nanomedicine, which can deliver both drugs simultaneously to the tumor site by controlling the concentration and ratio of the two drugs, is required.
Accordingly, the present invention provides an anticancer pharmaceutical composition comprising Doxorubicin and Irinotecan which inhibit topoisomerase 1 type 1 and Topoisomerase 2 which are overexpressed in cancer cells It has its purpose.
The present invention also relates to a method for producing an anticancer pharmaceutical composition comprising doxorubicin and irinotecan inhibiting topoisomerase-1 and topoisomerase-2, which are overexpressed in cancer cells There is another purpose in providing.
In order to attain the above object, the present invention provides a method for producing a polyethylene glycol-block-polyaspartic acid copolymer, which comprises adding 10 to 70 parts by weight of doxorubicin and 10 to 70 parts by weight of irinotecan to 100 parts by weight of a polyethylene glycol- Added mixture; And a biodegradable lipid coated with the mixture.
According to another aspect of the present invention, there is provided a method of preparing a core, the method comprising: forming a core by combining Doxorubicin and Irinotecan with a polyethylene glycol-block-polyaspartic acid copolymer; And coating the core with a biodegradable lipid. The present invention also provides a method for producing a pharmaceutical composition for anti-cancer.
Wherein the biodegradable lipid is selected from the group consisting of lecithin, hydrogenated phosphatidylcholine, dioloylphosphatidylcholine, distearoylphosphatidylcholine, myristoyl palmitoylphosphatidylcholine, myristoyl stearoylphosphatidylcholine, stearoyl palmitoylphosphatidylcholine, phosphatidylethanolamine, Phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylethanolamine, dimyristoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine and distearoylphosphatidylethanolamine.
10 to 70 parts by weight of doxorubicin and 10 to 70 parts by weight of irinotecan are added to 100 parts by weight of a polyethylene glycol-block-polyaspartic acid copolymer according to the present invention; And a biodegradable lipid coated with the mixture. The pharmaceutical composition for anticancer chemotherapy has pH-dependent release and sustained-release characteristics, and the topoisomerase-1 and topoisomerase- 2), as well as maximizing the efficacy of anticancer drugs in the treatment of cancer-resistant cancer cells.
1 is an image obtained by observing a polymer electrolyte composite nanoparticle (L-PCN / DI) encapsulated with doxorubicin and irinotecan coated with lecithin according to the present invention using a transmission electron microscope (TEM)
2 is a graph showing drug release of L-PCN / DI according to the present invention in a pH 5.0 (acetic acid buffer) and pH 7.4 (phosphate buffer) environment,
3 is a graph showing intracellular penetration of L-PCN / DI according to the present invention in various cancer cells by fluorescence intensity,
FIG. 4 is a graph showing the anticancer synergistic effect of L-PCN / DI according to the present invention in a cancer-induced mouse model.
The inventors of the present invention have found that, in combination chemotherapy regimens based on the maximal tolerated dose of two anticancer drugs, the ratio and ratio of the two drugs can be controlled so that the two drugs can be simultaneously delivered to the tumor site. Ratiometric nanomedicine, Researchers have developed nanoparticles coated with biodegradable lipids by forming core formed by combining Doxorubicin and Irinotecan with Polyethylene glycol-block-polyaspartic acid copolymer. Thereby completing the present invention.
The doxorubicin is represented by the following chemical formula 1, and is an anticancer agent called an anthracycline antitumor agent which is an anticancer agent that selectively acts on the cell cycle. The anticancer effect of doxorubicin is known to inhibit the enzyme called topoisomerase during cell replication and to interfere with cell division by interrupting the DNA structure by damaging the DNA structure.
The above doxorubicin may be used in the treatment of malignant lymphoma (lymphoma, Hodgkin's disease and non-Hodgkin's disease), gastrointestinal cancer (stomach cancer, liver cancer, rectum cancer, gall bladder cancer, colon cancer, pancreatic cancer), acute myelogenous leukemia, soft tissue osteosarcoma, Bronchial, bladder, or tumoral tumors.
The irinotecan is an anticancer agent that selectively acts on the cell cycle, and is represented by the following formula (2). The above irinotecan inhibits topoisomerase-1 (topoisomerase-1), inhibits DNA synthesis to inhibit cell division, and is mainly used for rectal cancer, colon cancer, stomach cancer, or lung cancer. Irinotecan itself has little cytotoxicity and must be converted to 7-ethyl-10-hydroxycamptothecin (SN-38) in vivo by carboxylesterase to become cytotoxic . SN-38 is glucuronide-linked and metabolized or excreted through bile excretion.
Accordingly, the present invention provides a composition comprising 10 to 70 parts by weight of doxorubicin and 10 to 70 parts by weight of irinotecan added to 100 parts by weight of a polyethylene glycol-block-polyaspartic acid copolymer; And a biodegradable lipid coated with the mixture. The present invention also provides a pharmaceutical composition for anti-cancer.
At this time, when the doxorubicin in the pharmaceutical composition according to the present invention is contained in an amount exceeding the above content range, side effects such as nausea, vomiting, cardiac arrhythmia and appendicitis may be intensified, and if it is contained in a small amount, Problems can arise.
In addition, when irinotecan is contained in an amount exceeding the above content range, problems such as shock, dyspnea, blood pressure lowering, septicemia, diarrhea and enteritis may be exacerbated. If the irinotecan is contained in a small amount, .
Wherein the biodegradable lipid is selected from the group consisting of lecithin, hydrogenated phosphatidylcholine, dioloylphosphatidylcholine, distearoylphosphatidylcholine, myristoyl palmitoylphosphatidylcholine, myristoyl stearoylphosphatidylcholine, stearoyl palmitoylphosphatidylcholine, phosphatidylethanolamine, Phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylethanolamine, dimyristoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine and distearoylphosphatidylethanolamine, and more preferably lecithin.
The pharmaceutical composition according to the present invention may comprise 10 to 70% by weight of the mixture and 30 to 70% by weight of the biodegradable lipid.
If the lecithin is contained in an excess amount beyond the content range, there may arise a problem that the drug is not released in a suitable environment. If the lecithin is contained in a small amount, the coating may be less and the release characteristic of the pharmaceutical composition may be lowered .
The pharmaceutical compositions according to the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the production of pharmaceutical compositions.
Examples of the carrier, excipient or diluent which can be used in the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose sucrose), lactose, gelatin, and the like.
In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
The dose of the pharmaceutical composition according to the present invention may vary depending on the age, sex and body weight of the patient, but doxorubicin is intravenously injected once a day from 60 mg /
Such dosage may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
In addition, doxorubicin and irinotecan, which constitute the pharmaceutical composition according to the present invention, have already been prescribed as an anticancer agent and thus have secured safety.
The composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, or intraperitoneally) depending on the intended method, and the dose may be appropriately determined depending on the body weight, age, sex, Diet. The range varies depending on the administration time, method of administration, excretion rate and severity of disease.
In addition, the present invention relates to a method for producing a core comprising the steps of: forming a core by combining Doxorubicin and Irinotecan with a polyethylene glycol-block-polyaspartic acid copolymer; And coating the core with a biodegradable lipid. The present invention also provides a method for producing a pharmaceutical composition for anti-cancer.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
Example 1 Preparation of Polymer Electrolyte Complex Nanoparticles (L-PCN / DI) Encapsulated with Lecithin Encapsulated with Doxorubicin and Irinotecan
First, a cationic drug is immobilized on the anion core of a polyethylene glycol-block-polyaspartic acid (PEG-b-PAsp) through electrostatic interactions to form a polymer electrolyte which encapsulates doxorubicin and irinotecan Polyelectrolyte complex nanoparticles (PCN) (PCN / DI) were prepared.
Doxorubicin (DOX) and irinotecan (IRI) were included in the PCN / DI at a weight ratio of 1: 1 and the weight ratio of PEG-b-PAsp to irinotecan (DOX / IRI) was 1: 1 Respectively. This resulted in nanoparticles with a small size (about 100 nm) and a uniform size distribution (PDI ~ 0.2).
To enhance the in vivo function and stability of the nanoparticles (PCN / DI), vesicles were formed around PCN / DI using Lecithin, known as biocompatible lipid.
100 mg of lecithin was dissolved in chloroform, and 100 mg of PCN / DI was mixed in a lecithin solution and homogenized using ultrasonic waves for 3 minutes to form L-PCN / DI. The organic solvent was evaporated and dispersed to form L-PCN / DI which is uniform nanoparticles of about 150 nm.
Polymer electrolyte composite nanoparticles (L-PCN / DI) encapsulated with doxorubicin and irinotecan coated with lecithin prepared as described above were confirmed by transmission electron microscope (TEM).
As a result, as shown in Fig. 1, a thin lipid membrane surrounding the nanoparticle core was confirmed. In addition, it was confirmed that the nanoparticles have a nanometer size of about 150 nm and the size distribution is also constant.
< Example 2> pH5 .0( Acetic acid buffer solution )and pH7 .4( Phosphate buffer ) Environment coated with lecithin according to the present invention Doxorubicin Irinotecan Determination of Drug Release Characteristics of Polymer Electrolyte Complex Nanoparticles (L-PCN / DI)
The drug releasing properties of the polymer electrolyte nanoparticles (L-PCN / DI) containing doxorubicin and irinotecan coated with lecithin prepared in Example 1 were measured using a dialysis membrane at pH 5.0 (acetic acid buffer) and pH 7.4 (phosphate buffer ).
Drug release of L-PCN / DI was measured using a Spectra / Pore 3500 Da-cut-off membrane tubing (Spectra / Por 3500) in PBS (pH 7.4, 0.14 M NaCl) and acetate- buffered saline (pH 5.4, 0.14 M NaCl) Da-cutoff membrane tubing).
Samples of the medium (0.5 mL) were collected at intervals and replaced with an equal volume of fresh buffer. The concentration of each drug was measured by high performance liquid chromatography (HPLC), expressed as a percentage of the total drug possible, and plotted as a function of time.
As a result, it was confirmed that the pH-dependent emission characteristic is shown in Fig. This mechanism induces drug release due to pH change in cancer cells, and it is considered that the efficiency of anticancer drug can be maximized in the treatment of cancer cells having drug resistance. In addition, the side effects can be considerably reduced.
< Example 3> In various cancer cell lines, L-PCN / Of DI Intracellular Confirm permeation
The degree of intracellular penetration of L-PCN / DI prepared in Example 1 was measured using a squamous cell cancer cell line (SCC-7) and a breast cancer cell line (MCF-7) or a resistant breast cancer cell line (MDA-MB-231 ) Using flow cytometry. 20 μg / mL of L-PCN / DI or drug cocktail solution was added to each cell and incubated for 30 minutes or 60 minutes. The fluorescence of doxorubicin was measured to determine the intracellular permeability of the nanoparticles.
As a result, as shown in Fig. 3, it was confirmed that endocytosis caused the migration to lysosomes in cancer cells and the permeation was good. Particularly, in MDA-MB-231 which is a resistant cancer cell, intracellular permeation of nanoparticles And it was confirmed that it increased further.
< Example 4 > cancer-induced mouse model of the L-PCN / DI Confirmation of anticancer effect after administration
In order to confirm the anticancer effect of the nanoparticles according to the present invention in a cancer-induced mouse model, a SCC-7 cancer cell-induced mouse model was first prepared.
All animal care and experimental protocols were performed according to the guidelines of the Animal Ethics Committee of Yeungnam University, Korea (Institutional Animal Ethical Committee, Yeungnam University, South Korea).
The tumor xenograft model was prepared by subcutaneously injecting 1 × 10 6 SCC7 cells (100 μL) into the thigh (lateral) of female BALB / c nude mice. When the tumor volume reached almost 100 mm 3 , Respectively.
In the SCC-7 cancer cell-induced mouse model prepared above, the irinotecan solution, doxorubicin solution, doxorubicin and irinotecan cocktail solution, or doxorubicin coated with lecithin prepared in Example 1 and irinotecan-containing nanoparticles were intravenously administered, The anticancer synergies of each treatment group for 30 days were evaluated. As a result, as shown in FIG. 4A, it was confirmed that the nanoparticles loaded with two kinds of anticancer drugs at a weight ratio of 1: 1 were superior to the drug cocktail solution.
In addition, irinotecan solution, doxorubicin solution, doxorubicin and irinotecan cocktail solution, polyelectrolyte complex nanoparticles (PCN / DI) encapsulated with doxorubicin and irinotecan, or doxorubicin coated with lecithin prepared in Example 1 in a SCC-7 cancer cell- (L-PCN / DI) containing irinotecan were intravenously administered. After about 30 days, the mice were euthanized using a CO 2 aspiration method, and the tumor was sampled and weighed. (B).
As a result, the polymeric electrolyte composite nanoparticles (PCN / DI) encapsulated with doxorubicin and irinotecan that were not coated with lecithin showed higher therapeutic effect than doxorubicin and irinotecan cocktail, but the lecithin-coated doxorubicin and irinotecan encapsulated polymer electrolyte complex (L-PCN / DI).
In summary, the present invention relates to a polymer electrolyte composite nanoparticle (L-PCN / DI) encapsulated with lecithin-coated doxorubicin and irinotecan, wherein the L-PCN / DI exhibits a higher intracellular permeability than the drug itself Showed higher therapeutic effect than doxorubicin and irinotecan cocktail.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (4)
Wherein the pharmaceutical composition comprises 10 to 70% by weight of the polymer electrolyte composite nanoparticles and 30 to 70% by weight of the lecithin.
And coating the polymer electrolyte composite nanoparticles with lecithin. ≪ RTI ID = 0.0 > 21. < / RTI >
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150051734A KR101769666B1 (en) | 2015-04-13 | 2015-04-13 | Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150051734A KR101769666B1 (en) | 2015-04-13 | 2015-04-13 | Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160122310A KR20160122310A (en) | 2016-10-24 |
| KR101769666B1 true KR101769666B1 (en) | 2017-08-21 |
Family
ID=57256522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150051734A KR101769666B1 (en) | 2015-04-13 | 2015-04-13 | Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101769666B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200086541A (en) | 2019-01-09 | 2020-07-17 | 경북대학교 산학협력단 | Sitosterol-doxorubicin derivatives for radiotherapy amplification, and composition for preventing or treating cancer diseases comprising the same |
| KR102618727B1 (en) | 2023-06-28 | 2023-12-28 | (주)바이오솔릭스 | Lipid nanoparticle for delivering nucleic acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003103822A2 (en) | 2002-06-01 | 2003-12-18 | Ethypharm | Stealth lipid nanocapsules, methods for the preparation thereof and use thereof as a carrier for active principle(s) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100390332B1 (en) | 2000-08-02 | 2003-07-07 | 유원민 | anti-cancer composition composed of anti-cancer and anti-malarial drugs |
-
2015
- 2015-04-13 KR KR1020150051734A patent/KR101769666B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003103822A2 (en) | 2002-06-01 | 2003-12-18 | Ethypharm | Stealth lipid nanocapsules, methods for the preparation thereof and use thereof as a carrier for active principle(s) |
Non-Patent Citations (2)
| Title |
|---|
| Journal of Biomedical Nanotechnology, 10(7), 1304-1312, 2014. |
| Journal of Controlled Release, 172, 852-861, 2013 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200086541A (en) | 2019-01-09 | 2020-07-17 | 경북대학교 산학협력단 | Sitosterol-doxorubicin derivatives for radiotherapy amplification, and composition for preventing or treating cancer diseases comprising the same |
| KR102618727B1 (en) | 2023-06-28 | 2023-12-28 | (주)바이오솔릭스 | Lipid nanoparticle for delivering nucleic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20160122310A (en) | 2016-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health | |
| Shen et al. | Versatile hyaluronic acid modified AQ4N-Cu (II)-gossypol infinite coordination polymer nanoparticles: multiple tumor targeting, highly efficient synergistic chemotherapy, and real-time self-monitoring | |
| Zhang et al. | Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats | |
| Zhao et al. | Challenges and potential for improving the druggability of podophyllotoxin-derived drugs in cancer chemotherapy | |
| Wahab et al. | Current trends and future perspectives of nanomedicine for the management of colon cancer | |
| Khan et al. | Co-delivery strategies to overcome multidrug resistance in ovarian cancer | |
| Yang et al. | MiRNA-204-5p and oxaliplatin-loaded silica nanoparticles for enhanced tumor suppression effect in CD44-overexpressed colon adenocarcinoma | |
| Xiao et al. | Structure-based design of charge-conversional drug self-delivery systems for better targeted cancer therapy | |
| Wang et al. | Curcumin-loaded TPGS/F127/P123 mixed polymeric micelles for cervical cancer therapy: formulation, characterization, and in vitro and in vivo evaluation | |
| Luiz et al. | Folic acid-modified curcumin-loaded liposomes for breast cancer therapy | |
| WO2011101859A1 (en) | A novel water soluble curcumin loaded nanoparticulate system for cancer therapy | |
| CN113350503B (en) | Carrier-free hybrid nano assembly and preparation method and application thereof | |
| Ren et al. | A unique highly hydrophobic anticancer prodrug self-assembled nanomedicine for cancer therapy | |
| Zhou et al. | Alternative and injectable preformed albumin-bound anticancer drug delivery system for anticancer and antimetastasis treatment | |
| WO2023030248A1 (en) | Dual-targeting biomimetic liposome containing elemene and cabazitaxel, and preparation method therefor and use thereof | |
| Lin et al. | Epigenetic inhibition assisted chemotherapeutic treatment of lung cancer based on artificial exosomes | |
| JP6229865B2 (en) | A micelle comprising an epirubicin-conjugated block copolymer and an anticancer agent, and a pharmaceutical composition applicable to the treatment of cancer or resistant cancer or metastatic cancer comprising the micelle | |
| CN106821987B (en) | Liposome carrying phenol hydroxyl group-containing insoluble drug, and preparation method and application thereof | |
| KR101769666B1 (en) | Anti-cancer pharmaceutical composition comprising doxorubicin and irinotecan and manufacturing method thereof | |
| CN112426535A (en) | Tumor-targeted drug nanocrystal delivery system | |
| Gupta et al. | Applications of lipid-engineered nanoplatforms in the delivery of various cancer therapeutics to surmount breast cancer | |
| Qian et al. | Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer | |
| Lin et al. | Tumor-targeted co-delivery of mitomycin C and 10-hydroxycamptothecin via micellar nanocarriers for enhanced anticancer efficacy | |
| CN108309940B (en) | β -elemene and platinum drug co-carried liposome and its preparation method | |
| WO2016014337A1 (en) | Drug delivery nanoemulsion systems |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant |