DRUG DELIVERY PLATFORMS COMPRISING SILK FIBROIN HYDROGELS AND USES THEREOF

1 . A drug delivery platform comprising a hydrogel, the hydrogel comprising:

a) a substantially sericin-depleted silk fibroin;

b) an amphiphilic peptide; and

c) an a compound having the structure of formula I

wherein each dashed line represents the presence or absence of a bond;

R 1 , R 2 and R 3 are each independently selected from H or C 1 -C 6 alkyl;

R 6 is CO 2 H, CO 2 R 7 , CON(R 7 ) 2 , CONHCH 2 CH 2 OH, CON(CH 2 CH 2 OH) 2 , CH 2 OR 7 , P(O)(OR 7 ) 2 ,

a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

R 7 is independently H, C 1 -C 6 alkyl or C 2 -C 6 alkenyl;

X and Y are each independently selected from H, OH, ═O, Cl, Br, I, or CF 3 ;

Z 1 and Z 2 are each independently selected from CH or N;

W 1 and W 2 are each independently selected from CH, CH 2 , aryl or substituted aryl, heteroaryl, substituted heteroaryl;

m is 0 to 4;

o is 0 to 6;

p is 0 or 1; and

V is C 1 -C 6 alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl.

2 . The drug delivery platform of claim 1 , wherein the hydrogel comprises about 1% (w/v) to about 10% (w/v) of silk fibroin.

3 . The drug delivery platform of claim 1 , wherein the amphiphilic peptide comprising a RGD motif or a non-RDG integrin.

4 . The drug delivery platform of claim 3 , wherein the amphiphilic peptide is 23 RGD.

5 . The drug delivery platform of claim 1 , wherein the amphiphilic peptide comprises of a tail region, followed by a spacer region and finally a RGD motif.

6 . The drug delivery platform of claim 1 , wherein the hydrogel comprises a molar ratio of 1:10 to 10:1 moles of the amphiphilic peptide per mole of the silk fibroin.

7 . The drug delivery platform of claim 6 , wherein the hydrogel comprises a molar ratio of 3:1 moles of the amphiphilic peptide per mole of the silk fibroin.

8 . The drug delivery platform of claim 1 , wherein the hydrogel comprises silk fibroin having a β-sheet conformation of at least 80%.

9 . The drug delivery platform of claim 1 , wherein the hydrogel comprises silk fibroin having a β-sheet conformation of at least 50%.

10 . The drug delivery platform of claim 1 , wherein the hydrogel comprises silk fibroin having a β-sheet conformation of at least 20%.

11 . The drug delivery platform of claim 1 , wherein the hydrogel comprises silk fibroin having an α-helical and random coil conformation of at most 20%.

12 . The drug delivery platform of claim 1 , wherein the compound has the structure of formula II

wherein each dashed line represents the presence or absence of a bond;

R 1 , R 2 and R 3 are each independently selected from H or C 1 -C 6 alkyl;

R 4 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

X and Y are each independently selected from H, OH, ═O, Cl, Br, I, or CF 3 ;

Z 1 and Z 2 are each independently selected from CH or N;

W 1 and W 2 are each independently selected from CH, CH 2 , aryl or substituted aryl, heteroaryl, substituted heteroaryl;

m is 0 to 4;

p is 0 or 1;

o is 0 to 4; and

V is C 1 -C 6 alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl.

13 . The drug delivery platform of claim 1 , wherein V is

wherein U is C, N, O, or S; R 5 is halogen, C 1 -C 6 alkyl, or C 2 -C 6 alkenyl; and n is 0-7.

14 . The drug delivery platform of claim 15 , wherein U is S; R 5 is F, Cl, Br, or I; and n is 1, 2, or 3.

15 . The drug delivery platform of claim 1 , wherein W 2 is thiophene.

16 . The drug delivery platform of claim 1 , wherein the compound has the structure of formula III

wherein each dashed line represents the presence or absence of a bond;

R 1 , R 2 and R 3 are each independently selected from H or C 1 -C 6 alkyl;

R 4 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

W 1 and W 2 are each independently selected from CH, CH 2 , aryl or substituted aryl, heteroaryl, substituted heteroaryl;

m is 0 to 4;

o is 0 to 4;

p is 0 or 1; and

V is CH 3 , aryl, aryl or substituted aryl, heteroaryl, substituted heteroaryl.

17 . The drug delivery platform of claim 1 , wherein the compound has the structure of formula IV

wherein each dashed line represents the presence or absence of a bond;

R 1 , R 2 and R 3 are each independently selected from H or C 1 -C 6 linear alkyl;

R 4 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

m is 0 to 4;

o is 0 to 4;

p is 0 or 1; and

V is CH 3 , aryl, aryl or substituted aryl, heteroaryl, substituted heteroaryl.

18 . The drug delivery platform of claim 1 , wherein the compound has the structure of formula V

wherein each dashed line represents the presence or absence of a bond;

R 4 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

o is 0 to 4; and

V is CH 3 , aryl, aryl or substituted aryl, heteroaryl, substituted heteroaryl.

19 . The drug delivery platform of claim 1 , wherein the compound is

a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof.

20 . The drug delivery platform of claim 1 , wherein the compound is

a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof.

21 . The drug delivery platform of claim 1 , wherein the hydrogel further comprises an alginate, a polyalkylene oxalate, a polyamide, a polyamidoester, a polyanhydride, a polycarbonate, a polyester, a polyethylene glycol, a polyhydroxyaliphatic carboxylic acid, a polyorthoester, a polyoxaester, a polypeptide, a polyphosphazene, a polysaccharide, a polyurethane, or any combination thereof.

22 . The drug delivery platform of claim 21 , wherein the polysaccharide is a cellulose, an agarose, an elastin, a chitosan, a chitin, or a glycosaminoglycan.

23 . The drug delivery platform of claim 22 , wherein the glycosaminoglycan is a chondroitin sulfate, a dermatan sulfate, a keratan sulfate, or a hyaluronic acid.

24 . The drug delivery platform of claim 21 , wherein the polyester is a D-lactic acid, a L-lactic acid, a racemic lactic acid, a glycolic acid, or a caprolactone.

25 . The drug delivery platform of claim 1 , wherein the platform is an extended drug release platform.

26 . The drug delivery platform of claim 25 , wherein the extended drug release platform releases a pharmaceutically-active drug with substantially first order release kinetics over a period of at most 6 days after administration

27 . The drug delivery platform of claim 1 , wherein the platform is a sustained drug release platform.

28 . The drug delivery platform of claim 27 , wherein the sustained drug release platform releases a pharmaceutically-active drug with substantially first order release kinetics over a period of at least 45 days after administration.

29 . The drug delivery platform of claim 1 , wherein the hydrogel is processed into particles.

30 . The drug delivery platform of claim 30 , wherein the hydrogel particles are combined with a carrier.

31 . The drug delivery platform of claim 31 , wherein the hydrogel particle-carrier combination is processed into a solution, oil, lotion, gel, ointment, cream, slurry, salve, or paste.

32 . A method of treating glaucoma in an individual, the method comprising the step of administering a drug delivery platform of claim 1 into an eye of the individual, wherein administration reduces a symptom associated with glaucoma, thereby treating the glaucoma.

33 . A method of treating elevated intraocular pressure in an individual, the method comprising the step of administering a drug delivery platform of claim 1 into an eye of the individual, wherein administration reduces intraocular pressure, thereby treating the elevated intraocular pressure.

34 . A method of treating corneal haze or opacity in an individual, the method comprising the step of administering a drug delivery platform of claim 1 into an eye of the individual, wherein administration reduces a symptom associated with corneal haze or opacity, thereby treating the corneal haze or opacity.

35 . A method of treating inflammatory bowel disease in an individual, the method comprising the step of administering a drug delivery platform of claim 1 to the individual, wherein administration reduces a symptom associated with inflammatory bowel disease, thereby treating the inflammatory bowel disease.

36 . A method of treating a wound in an individual, the method comprising the step of administering a drug delivery platform of claim 1 to the wound of the individual, wherein administration promotes healing of the wound or reduced scaring, thereby treating the wound.

37 . A drug delivery platform comprising:

a) a substantially sericin-depleted silk fibroin;

b) an amphiphilic peptide; and

c) an a compound having the structure of formula I

wherein each dashed line represents the presence or absence of a bond;

R 1 , R 2 and R 3 are each independently selected from H or C 1 -C 6 alkyl;

R 6 is CO 2 H, CO 2 R 7 , CON(R 7 ) 2 , CONHCH 2 CH 2 OH, CON(CH 2 CH 2 OH) 2 , CH 2 OR 7 , P(O)(OR 7 ) 2 ,

a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable amine salt thereof;

R 7 is independently H, C 1 -C 6 alkyl or C 2 -C 6 alkenyl;

X and Y are each independently selected from H, OH, ═O, Cl, Br, I, or CF 3 ;

Z 1 and Z 2 are each independently selected from CH or N;

W 1 and W 2 are each independently selected from CH, CH 2 , aryl or substituted aryl, heteroaryl, substituted heteroaryl;

m is 0 to 4;

o is 0 to 6;

p is 0 or 1; and

V is C 1 -C 6 alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl.

38 . The drug delivery platform of claim 37 , wherein the platform is processed into a hydrogel, a sheet, a film, a porous material, a fiber, a thread, a microsphere, a mesh, or a solid.