WO2013072686A2

WO2013072686A2 - Self-assembling peptides

Info

Publication number: WO2013072686A2
Application number: PCT/GB2012/052830
Authority: WO
Inventors: Janice Anson; Agnieszka MILEWSKA-ZUK; Alberto Saiani; Claire TANG; Robyn WALKER
Original assignee: University of Manchester; Reckitt and Colman Overseas Ltd
Current assignee: University of Manchester; Reckitt and Colman Overseas Ltd
Priority date: 2011-11-18
Filing date: 2012-11-15
Publication date: 2013-05-23
Anticipated expiration: 2014-05-18
Also published as: GB201119910D0; WO2013072686A3; GB2496654A

Abstract

The present invention is directed to peptide-based hydrogels in which the peptides coalesce such that they 'self-assemble' to form a hydrogel. Such hydrogels can be used to deliver pharmaceutically active compounds through mucosal tissue. The peptides have 2- 20 amino acids. Preferred peptides have 6 - 10 amino acids. The peptides have been found to adhere well to mucosal tissue allowing for good delivery of pharmaceutically active compounds.

Description

Self - Assembling Peptides

The present invention is directed to peptide-based hydrogels. In particular, the present invention is directed to peptide-based hydrogels in which the peptides coalesce such that they 'self-assemble' to form a hydrogel. Such hydrogels can be used to deliver pharmaceutically active compounds through mucosal tissue.

Peptides are short polymers of amino acids wherein the amino acids are connected by peptide bonds and have an amino group at one end and a carboxylic acid group at the other end. The shortest peptide is a dipeptide. A sequence of peptides can be built up to form a polypeptide. Polypeptides themselves are used to form proteins.

Polypeptides are known to commonly form alpha-helices and beta-sheets. Indeed, polypeptides can be specifically designed to self-assemble into alpha-helices and beta- sheets by taking advantage of biomolecular properties, intramolecular folding, the secondary structure, any electrostatic interactions and amphiphilicty.

Most of the work done in this area relates to the use of these materials to form gels which are potentially useful in film forming or biomaterials that can be used in applications such as artificial skin and separation matrices.

US 2005/0181973 discloses self-assembling peptides that include an additional domain that does not self-assemble. These materials are useful in the area of cell culture, tissue engineering and tissue repair. US 2009/0162437 discloses self- assembling peptides that have an additional domain that does not self-assemble.

US 5 670 483 discloses a self-assembling peptide which has at least 12 amino acids. The peptides are used to form stable macroscopic membranes. US 5 955 343 also discloses polypeptides that can form stable macroscopic membranes. In this case the oligopeptides are related to a yeast DNA binding protein, zuotin.

US 2002/0160471 teaches of a polypeptide scaffold having a 3-dimensional arrangement of predetermined geometry. There is no disclosure in the prior art regarding the use of such peptides for the preparation of formulations for delivery of an active to mucosal tissue, such as the mouth/oral cavity, throat, oesophagus, trachea, lungs, ear, eye, vagina and/or rectum. According to a first aspect of the present invention there is provided a pharmaceutical composition comprising at least one pharmaceutically active compound and at least one peptide having 2 - 20 amino acids that is capable of mediating self-assembly.

Preferably the peptide has 6 - 12 amino acids. More preferably the peptide has 8 amino acids.

Preferably the one or more amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, isoleucine, aspartic acid and glutamic acid. Preferably the peptides comprise at least one amino acid having a hydrophobic side chain (a hydrophobic amino acid), and at least one amino acid having a hydrophilic side chain (a hydrophilic amino acid).

Typically the peptide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.

The concentration of peptide in the composition can be 0.1 - 10% w/w. Typically, the concentration is 0.5 - 5% w/w. A more typical concentration is 1 - 3% w/w. In an embodiment of the invention, the hydrophobic amino acids are selected from the group consisting of phenylalanine, valine, leucine and isoleucine and the hydrophilic amino acids are selected from the group consisting of arginine, lysine, aspartic acid and glutamic acid. In a first preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys or Phe- Glu-Phe-Lys-Phe-Glu-Phe-Lys. In a second preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and arginine (Arg). In a more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg- Phe-Arg.

In a third preferred embodiment the hydrophobic amino acid can be selected to be valine (Val) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In a more preferred embodiment the amino acid sequence of the peptide is Val-Glu-Val-Glu-Val-Lys-Val-Lys or Val-Glu-Val-Lys- Val-Glu-Val-Lys.

In a fourth preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu- Phe-Arg-Phe-Lys, Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg, or Phe-Glu-Phe-Arg-Phe- Arg-Phe-Lys.

The pharmaceutically active compound present in the pharmaceutical compositions of the present invention may be any pharmaceutically active agent that is suitable for mucosal delivery. For example, the pharmaceutically active compound may be selected from one or more of the following categories of pharmaceutically active compounds: anti-cancer agents, antibacterial agents, antifungal/yeast agents, antimicrobial peptides, anti-inflammatory agents, antihistamine agents, antiseptic agents, decongestants, local anaesthetic agents, ophthalmic agents (e.g. drugs to treat glaucoma or other eye disorders), cough suppressants, expectorants, prebiotics and probiotics.

In a particular embodiment, the at least one pharmaceutically active compound can be selected from the group consisting of 2,4-dichlorobenzyl alcohol (DCBA), amyl metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, cetylpyridinium chloride, dequalinium chloride, menthol, ambroxol hydrochloride, dextromethorphan hydrobromide, phenylephrine and guaifenesin. Preferably the at least one pharmaceutically active compound is selected from the group comprising 2,4-dichlorobenzyl alcohol (DCBA), amyl metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, prebiotics (such as oligofructose, inulin and others), probiotics (such as L. acidophilus, L. reuteri, L. rhamnosus, L. casei, L. paracasei, L. plantarum group, L. brevis, L. fermentum, L. salivarius, Streptococcus salivarius, B. bifidum, B. longum, B. lactis, B. infantis, Bacillus Coagulans and others), natural extracts and herbs (aloe vera, sage, thyme, sandalwood, niaouli, nigella sativia, echinacea, tea tree, propolis, hyssop, peppermint, slippery elm, elderberry, coltsfoot, eucalyptus oil, chamomile oil, rosemary extracts, citrus extract, cardamom and others), cooling ingredients (e.g. menthol), warming ingredients and any other beneficial agents. More preferred pharmaceutically active compounds are flurbiprofen, lidocaine and benzocaine. At least one pharmaceutically active compound can be present at a level of 0.1 - 10% w/w. Typically, the concentration is 1 - 2% w/w.

The composition can be in the form of a lozenge, a liquid-filled lozenge, a liquid, a syrup, a powder, a tablet, a chewable tablet, a spray, a gel, a capsule, a pastille, a mouthwash, a jelly, a chew or a gum.

According to a second aspect of the present invention there is provided a peptide having 4 - 16 amino acids that is capable of mediating self-assembly wherein the amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, isoleucine, aspartic acid and glutamic acid.

Preferably the peptide has 6 - 10 amino acids. More preferably the peptide has 8 amino acids. Preferably the peptide comprises at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilic side chain.

Typically the peptide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids. In an embodiment of the invention, the hydrophobic amino acids are selected from the group consisting of phenylalanine, valine, leucine and isoleucine and the hydrophilic amino acids are selected from the group consisting of arginine, lysine, aspartic acid and glutamic acid.

In a first preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys or Phe- Glu-Phe-Lys-Phe-Glu-Phe-Lys.

In a second preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and arginine (Arg). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg- Phe-Arg or Phe-Glu-Phe-Arg-Phe-Glu-Phe-Arg.

In a third preferred embodiment the hydrophobic amino acid can be selected to be valine (Val) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In a more preferred embodiment the amino acid sequence of the peptide is Val-Glu-Val-Glu-Val-Lys-Val-Lys or Val-Glu-Val-Lys- Val-Glu-Val-Lys In a fourth preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu- Phe-Arg-Phe-Lys, Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg, or Phe-Glu-Phe-Arg-Phe- Arg-Phe-Lys.

According to a third aspect of the present invention there is provided a hydrogel/ viscous liquid comprising more than one of the peptides as described in the second aspect of the present invention wherein the more than one peptides form a matrix that is hydrated to form said gel/viscous liquid. The matrix can be in the form of a beta- sheet.

According to a fourth aspect of the present invention there is provided a method of treating pain, inflammation, and infection of the oral cavity of an individual which comprises administering to an individual a composition as described in the first aspect of the present invention. Typically the composition is administered to an individual having a sore throat. According to a fifth aspect of the present invention there is provided the use of a composition as described in the first aspect of the present invention for the treatment of a sore throat in an individual.

According to a sixth aspect of the present invention there is provided the a composition as described in the first aspect of the present invention for use in the treatment of an eye infection or disorder.

According to an seventh aspect, the present invention provides a method of treating an eye infection or disorder in an individual in need of such treatment, the method comprising administering a therapeutically effective amount of a composition as defined in the first aspect of the present invention.

According to an eighth aspect of the present invention there is provided the a composition as described in the first aspect of the present invention for use in the treatment of an ear infection or disorder.

According to an ninth aspect, the present invention provides a method of treating an eye infection or disorder in an individual in need of such treatment, the method comprising administering a therapeutically effective amount of a composition as defined in the first aspect of the present invention.

According to a tenth aspect of the present invention there is provided a composition as described in the first aspect of the present invention that is substantially water free and forms a hydrogel/viscous liquid upon the addition of water. According to a eleventh aspect of the present invention there is provided the use of a composition as described in the first aspect of the present invention for the delivery of a drug through any mucosal tissue in an individual.

The mucosal tissue may be selected from mucosal tissues present in the mouth, throat, oesophagus, trachea, lungs, ear, eye, vagina and/or rectum.

As used herein the term 'pharmaceutically active compound' covers pharmaceutically active compounds and pharmaceutically acceptable salts and esters thereof.

Example embodiments of the present invention will now be described, with reference to the accompanying Figure (Figure 1) which illustrates an In- Vitro Oral Retention (IVOR) model used to simulate the flow of the composition over a mucosal surface.

Compositions were prepared in the following way.

The required amount of octapeptide was suspended in HPLC grade water (either 100% or 70% of the final volume required) to obtain the desired concentration (10- 40 mg ml/¹). To dissolve the peptide the sample was vortexed, sonicated and left at 80-85 °C for a period of up to several hours depending on the peptide sequence and its concentration. The pH of the sample was not adjusted, resulting in samples with final pH values of ca. 2-3 (depending on the peptide concentration due to residual TFA). The samples were then cooled and maintained at room temperature for ~ 12 hours (overnight) to enable gelation.

Actives were loaded differently depending on their solubility in ethanol. Insoluble actives such as flurbiprofen were added as powder on top of the gel/viscous solution formed, either followed by ethanol (30% of the final volume required) or added to gel/viscous solution fully water based (100% of water in the final formula) to form a suspension. Soluble actives such as lidocaine hydrochloride monohydrate were either pre-dissolved in ethanol (30% of the final volume required) and added to the gel/viscous solution formed or added as powder on top of the gel/viscous solution formed. To ensure homogeneous samples were obtained, the samples were vortexed and sonicated immediately after the active loading. The samples were then maintained at room temperature for ~ 12 hours (overnight) to allow them to settle. The final pH of the sample can be adjusted to pH 4-7 using sodium hydroxide solutions (5 M, e.g. 5-20 μΐ, for 30 mg mlT¹ samples of Phe-Glu-Phe-Glu-Phe-Lys- Phe-Lys) after ~ 6 hours.

At any step the air bubbles resulting from the sample mixing could be removed by centrifugating the samples at 1000 rpm for 30-60 seconds. The peptides were used with different active ingredients as detailed in the following examples.

Examples 1 and 2

Example 1 and 2 compositions (peptides and flurbiprofen as the active ingredient) are detailed in Table 1.

Table 1.

The retention profiles of the hydrogel compositions containing flurbiprofen at a concentration of 16.2 mg/ml were determined. The retention profiles were determined from the calculation of flurbiprofen concentration from each time point using the IVOR model shown in Figure 1. The IVOR model is an in- vitro mucosa testing model that was used in this study to test samples' adhesion properties to mucosa and actives' release/retention profile over set period of time. The main part of it is a moveable ramp, the slope of which can be modified to mimic different conditions. It is also possible to maintain constant temperature of the model during a test. Visking membrane, which is semi- or partially permeable cellulose based membrane, was used to mimic mucosa surface.

For samples with flurbiprofen, the membrane/tissue was pre-soaked in artificial saliva and conditioned on the slope, which was set at 30°, of the IVOR model for 15 minutes with a flow rate of 2ml/min of artificial saliva. The flow was then stopped and ΙΟΟμΙ of sample was applied to the top of the slope and left for one minute. The flow was then re-started and the eluate was collected over ten minute intervals for one hour. Each 10 minute sample was collected in a 50ml volumetric flask, each sample was made up to the required volume with methanol. The samples were analysed using HPLC. The HPLC was set up as follows:

Column: Zorbax Eclipse XDB-C18, 150 x 4.6mm 5μ or equivalent

Phase: 660 ml methanol : 340 ml deionised water : 1ml ortho-phosphoric acid

Flow rate: 1.5 ml/min

Wave length: 280nm 4BW ref 600nm 100BW

Run time: 10 minutes

Column temperature: 25°C

Injection: 80μ1

The maximum amount of flurbiprofen present in a collected sample is 1.62 mg in 50 ml or 0.032 mg/ml. A graph was plotted for peak area against concentration of flurbiprofen. Graph 1 shows the concentration levels to be linear over the range 0.002 to 0.07 mg/ml. Flurbiprofen _y = 49639x + 6.2149

R² = 1

Concentration (mg/ml)

Graph 1 : Plot of area against concentration of flurbiprofen.

Graph 1 represents a calibration curve, which was generated using standards of known amount of flurbiprofen. It shows that the amount of flurbiprofen was linear over the concentration range 0.002 to 0.07 mg/ml. Therefore, this graph was used to determine the amount of flurbiprofen in an unknown sample (collected eluate from the test) by comparing the unknown to a set of standard samples of known active amount. In example 1 the amount of flurbiprofen remaining on the slope after 10 minutes is 26.3% (0.36mg). This decreased to 1.6% (0.02mg) after 60 minutes based on actual recovery. Recoveries ranged from 81 to 86% based on a theoretical value of 1.63 mg/ml. In example 2 the amount of flurbiprofen remaining on the slope after 10 minutes is 47.3% (0.67mg). This decreased to 6.1% (0.09mg) after 60 minutes. Recoveries ranged from 83 to 88% based on a theoretical value of 1.64 mg/ml.

As a control, a lozenge was applied to the slope. The lozenge sample was applied over 6 minutes (representing someone sucking the lozenge).

A comparison between the lozenge and peptide compositions is shown in Graph 2. This does not account for the initial flurbiprofen loading amount.

10 20 30 40 50 60

Time (min)

Graph 2: Comparison between flurbiprofen retention profiles for Examples 1 (Phe- Glu-Phe-Glu-Phe-Lys-Phe-Lys - FEFEFKFK) & 2 (Phe-Glu-Phe-Glu-Phe-Arg-Phe- Arg - FEFEFRFR), and a lozenge.

This comparison shows the peptide compositions retaining the greatest percentage of flurbiprofen on the slope.

Examples 3 and 4

Example 3 and 4 compositions (peptides and active ingredient) are detailed in Table

Examples 3 and 4 use the peptide of Example 1 above (FEFEFKFK) but lidocaine is used in Example 3 and benzocaine is used in Example 4 as an alternative active ingredient to flurbiprofen. Table 2.

The retention profiles of the hydrogel compositions containing Lidocaine or Benzocaine at a concentration of 7.4 mg ml and 20 mg/ml respectively were determined. The retention profiles were determined from the calculation of lidocaine or benzocaine concentration from each time point using the IVOR model shown in Figure 1 and as detailed above for Examples 1 and 2. For samples with lidocaine and benzocaine, the membrane/tissue was pre-soaked and the IVOR model run in the same way as detailed above for Examples 1 and 2 which used flurbiprofen.

The samples for Example 3 (lidocaine) were analysed using HPLC. The UPLC was set up as follows:

Column: Waters Spherisorb S5 SCX, 100 x 4.6mm x 30mm long guard

cartridge or equivalent.

Phase: 600 ml Acetonitrile : 400 ml buffer

Buffer: Dissolve lg potassium dihydrogen orthophosphate in 200ml of water.

Add 6ml of orthophosphoric acid and dilute to 2 litre with water.

Adjust the pH to 2.5 with ammonia.

Flow rate: 2.0 ml/min Wave length : 21 Onm 4B W ref 360nm 1 OOB W

Run time: 8 minutes

Column temperature: 35°C

Injection: 20 μΐ

The samples for Example 4 (benzocaine) were analysed using HPLC The HPLC was set up as follows:

Column: Waters Symmetry C8, 5 ηι, 3.9mm x 150mm or equivalent.

Phase: 250 ml Acetonitrile : 750 ml buffer

Buffer: Dissolve 6.8g potassium dihydrogen orthophosphate in 1000ml of water.

Adjust the pH to 2.5 with orthophosphoric acid.

Flow rate: 1.5 ml/min

Wave length : 288nm 4B W ref 360nm 100B W

Run time: 10 minutes

Column temperature: 40°C

Injection: 50μ1

The maximum amount of lidocaine or benzocaine present in a collected sample is 0.74 mg in 50 ml or 0.0148 mg/ml and 2 mg in 50 ml or 0.048 mg/ml respectively. A graph was plotted for peak area against concentration of lidocaine or benzocaine respectively.

Graph 3 shows the concentration levels to be linear over the range 0.007 to 0.07 mg/ml for lidocaine.

Lidocaine ^y = 37065x + 6.4685

A ₍A_)reamu R² = 0.9999

0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08

Concentration (mg/ml)

Graph 3 : Plot of area against concentration of lidocaine for Example 3.

Graph 3 represents a calibration curve, which was generated using standards of known amount of lidocaine. It shows that the amount of lidocaine was linear over the concentration range 0.007 to 0.07 mg/ml. Therefore, this graph was used to determine the amount of lidocaine in an unknown sample (collected eluate from the test) by comparing the unknown to a set of standard samples of known active amount. In example 3 the amount of lidocaine remaining on the slope after 10 minutes is about 73.130% (25 mg). This decreased to is about 44% (0.15 mg) after 60 minutes based on actual recovery; a recovery of 45% based on a theoretical value of 0.74 mg/ml. This is shown below in Graph 4 below.

Lidocaine 30mg/ml Drip Test

30 50 60

Graph 4: Retention profile of example 3 (FEFEFKFK) 30mg/ml with 7.4mg/ml lidocaine This shows that the compositions of Example 3 retain a very good percentage of lidocaine on the slope after 10 minutes and even after 60 minutes.

Graph 5 shows the concentration levels to be linear over the range about 0.002 to 0.07 m /ml for benzocaine.

Graph 5: Plot of area against concentration of benzocaine for Example 5

Graph 5 represents a calibration curve, which was generated using standards of known amount of benzocaine. It shows that the amount of benzocaine was linear over the concentration range about 0.002 to 0.07 mg/ml. Therefore, this graph was used to determine the amount of benzocaine in an unknown sample (collected eluate from the test) by comparing the unknown to a set of standard samples of known active amount.

In example 4 the amount of benzocaine remaining on the slope after 10 minutes is about 85% (exact amount and mg please). This decreased to is about 70% (exact amount and mg please) after 60 minutes based on actual recovery. Recoveries ranged from 12 to 46% based on a theoretical value of 12 0 mg/ml. This is shown below in Graph 5 below.

30mg/ml HG

10 20 30 40 50 60

Tim e (m ins)

Graph 5: Retention profile of example 4 (FEFEFKFK) 30mg/ml with 20 mg/ml benzocaine

This shows that the compositions of Example 4 retain a very good percentage benzocaine on the slope after 10 minutes and even after 60 minutes. Example 5

Example 5 comprising another peptide, FEFKFEFK (Phe-Glu-Phe-Lys- Phe-Glu- Phe-Lys) at a concentration of 30 mg/ml was produced used in the same way as described above for Examples 1-4.

The example was tested for mucoadhesive properties using a static model constituted of a glass slide covered with a permeable membrane (12000-14000 Da) placed in a sealed container. 400 uL samples were pipetted onto the membrane and left to settle down for 10 minutes before being covered with 10 mL of solution (artificial saliva or water). The behaviour of the systems in the presence of excess solvent was then observed at different time points. In both water and artificial saliva excess, weak gels of FEFKFEFK (30 mg mL-1) were found to adhere to the membrane after 2 minutes. Complete dissolution of the peptide gel was observed after 16 hours in water. However in the presence of artificial saliva the gel layer remained adhered onto the membrane after the same time. Unlike FEFEFKFK, the gel was not found to swell in these conditions.

Thus the peptide FEFKFEFK was found to have similar mucoadhesive properties to the peptide FEFEFKFK.

An advantage of the present invention is that there is provided a pharmaceutical composition that exhibits excellent retention properties for an active compound on a mucosal surface.

Further modifications and improvements can be made without departing from the scope of the invention described herein.

Claims

A pharmaceutical composition comprising at least one pharmaceutically active compound and a peptide having 2- 20 amino acids that is capable of mediating self-assembly.

A pharmaceutical composition as claimed in Claim 1 wherein the peptide has 6 - 10 amino acids.

A pharmaceutical composition as claimed in Claim 2 wherein the peptide has 8 amino acids.

A pharmaceutical composition as claimed in any of the preceding Claims wherein the one or more amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, isoleucine, aspartic acid and glutamic acid.

A pharmaceutical composition as claimed in any of the preceding Claims wherein the peptides comprise at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilic side chain.

A pharmaceutical composition as claimed in Claim 5 wherein the peptide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.

A pharmaceutical composition as claimed in any of the preceding Claims wherein the concentration of peptide in the composition is 0.1 - 10% w/w.

A pharmaceutical composition as claimed in Claim 7 wherein the concentration is 0.5 - 5% w/w.

A pharmaceutical composition as claimed in Claim 8 wherein the concentration is 1 - 3 w/w%.

A pharmaceutical composition as claimed in any of the preceding Claims wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).

A pharmaceutical composition as claimed in Claim 10 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys.

A pharmaceutical composition as claimed in Claim 10 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Lys-Phe-Glu-Phe-Lys.

A pharmaceutical composition as claimed in any of Claims 1 - 9 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and arginine (Arg).

A pharmaceutical composition as claimed in Claim 13 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Arg.

A pharmaceutical composition as claimed in Claim 13 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Glu-Phe-Arg.

A pharmaceutical composition as claimed in any Claims 1 - 9 wherein the hydrophobic amino acid is selected to be valine (Val) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).

A pharmaceutical composition as claimed in Claim 16 wherein the amino acid sequence of the peptide is Val-Glu-Val-Glu-Val-Lys-Val-Lys.

A pharmaceutical composition as claimed in Claim 16 wherein the amino acid sequence of the peptide is Val-Glu-Val-Lys-Val-Glu-Val-Lys.

A pharmaceutical composition as claimed in any Claims 1 - 9 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg).

A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Lys.

A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg.

A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Arg-Phe-Lys.

A pharmaceutical composition as claimed in any of the preceding Claims wherein the at least one pharmaceutically active compound is a cancer drug, anti-bacterial or anti-microbial drug/peptide, an antibiotic and antiinflammatory drug, and anti-yeast infection drug, anti-histaminic drug or selected from the group consisting of 2,4-dichlorobenzyl alcohol (DCBA), amyl metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, cetylpyridinium chloride, dequalinium chloride, menthol, ambroxol hydrochloride, dextromethorphan hydrobromide, phenylephrine, guaifenesin, prebiotics (such as oligofructose, inulin and others), probiotics (such as L. acidophilus, L. reuteri, L. rhamnosus, L. casei, L. paracasei, L. plantarum group, L. brevis, L. fermentum, L. salivarius, Streptococcus salivarius, B. bifidum, B. longum, B. lactis, B. infantis, Bacillus Coagulans and others), natural extracts and herbs (aloe vera, sage, thyme, sandalwood, niaouli, nigella sativia, echinacea, tea tree, propolis, hyssop, peppermint, slippery elm, elderberry, coltsfoot, eucalyptus oil, chamomile oil, rosemary extracts, citrus extract, cardamom and others), cooling ingredients (e.g. menthol), warming ingredients and any other beneficial agents.

A pharmaceutical composition as claimed in Claim 23 wherein the at least one pharmaceutically active compound is selected from the group comprising 2,4- dichlorobenzyl alcohol (DCBA), amyl metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine.

A pharmaceutical composition as claimed in Claim 24 wherein the pharmaceutically active compound is selected from lidocaine, benzocaine or flurbiprofen.

A pharmaceutical composition as claimed in any the preceding Claims wherein the at least one pharmaceutically active compound is present at a level of is 0.1 - 10% w/w.

A pharmaceutical composition as claimed in Claim 26 wherein the at least one pharmaceutically active compound is present at a level of is 1 - 2% w/w.

A pharmaceutical composition as claimed in any the preceding Claims wherein the composition is in the form of a lozenge, a liquid-filled lozenge, a liquid, a syrup, a powder, a tablet, a chewable tablet, a spray, a gel, a capsule, a mouthwash, a jelly, a chew, a pastille or a gum.

A peptide having 2 - 20 amino acids that is capable of mediating self- assembly wherein the amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, isoleucine, aspartic acid and glutamic acid.

A peptide as claimed in Claim 29 wherein the peptide has 6 - 10 amino acids.

A peptide as claimed in Claim 30 wherein the peptide has 8 amino acids.

A peptide as claimed in any of Claims 29 - 31 wherein the peptide comprises at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilic side chain.

A peptide as claimed in Claim 32 wherein the peptide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.

A peptide as claimed in any of Claims 29 - 33 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).

A peptide as claimed in Claim 34 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys.

A peptide as claimed in Claim 34, wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Lys-Phe-Glu-Phe-Lys.

A peptide as claimed in any of Claims 29 - 33 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and arginine (Arg).

A peptide as claimed in Claim 37 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Arg

A peptide as claimed in Claim 37 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Glu-Phe-Arg.

A peptide as claimed in any of Claims 29 - 33 wherein the hydrophobic amino acid is selected to be valine (Val) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).

A peptide as claimed in Claim 40 wherein the amino acid sequence of the peptide is Val-Glu-Val-Glu-Val-Lys-Val-Lys.

A peptide as claimed in Claim 40 wherein the amino acid sequence of the peptide is Val-Glu-Val-Lys-Val-Glu-Val-Lys.

A peptide as claimed in any of Claims 29 - 33 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg).

44. A peptide as claimed in Claim 43 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Lys.

45. A peptide as claimed in Claim 43 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg.

46. A peptide as claimed in Claim 43 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Arg-Phe-Lys.

47. A hydrogel or viscous liquid comprising more than one of the peptides of Claims 29 - 46 wherein the more than one peptide form a matrix of beta sheets that are hydrated to form said gel or viscous liquid.

48. A method of treating pain, inflammation, and infection of the oral cavity of an individual which comprises administering to an individual a composition as claimed in any of Claims 1 - 28.

49. A method as claimed in Claim 48 wherein the composition is administered to an individual having a sore throat.

50. A method for the delivery of a drug through mucosal tissue which comprises administering to an individual a composition as claimed in any of Claims 1 -

28.

51. The use of a composition as claimed in any of Claims 1 - 28 for the treatment of a sore throat in an individual.

52. A composition as claimed in any of Claims 1 - 28 that is substantially water free and forms a hydrogel or viscous liquid on addition of water.