Drug Delivery Platforms Comprising Silk Fibroin Hydrogels and Uses Thereof

1 . A drug delivery platform comprising:

a) a substantially sericin-depleted silk fibroin;

b) an amphiphilic peptide; and

c) 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′ 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-RGD integrin.

4 . 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 or a molar ratio of 3:1 moles of the amphiphilic peptide per mole of the silk fibroin.

5 . The drug delivery platform of claim 1 , wherein the hydrogel comprises silk fibroin having a β-sheet conformation of at least 20%, at least 50%, or at least 80%.

6 . 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%.

7 . 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.

8 . 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.

9 . The drug delivery platform of claim 8 , wherein U is S; R 5 is F, Cl, Br, or I; and n is 1, 2, or 3.

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

11 . 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.

12 . 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.

13 . 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.

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

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

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

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

16 . The drug delivery platform of claim 1 , wherein the platform is an extended drug release platform or a sustained drug release platform.

17 . The drug delivery platform of claim 16 , 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

18 . The drug delivery platform of claim 16 , 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.

19 . The drug delivery platform of claim 1 , wherein the platform is processed into a hydrogel, a sheet, a film, a porous material, a fiber, a thread, a solution, an oil, a lotion, a gel, an ointment, a cream, a slurry, a salve, a paste, a microsphere, a mesh, a mat, or a solid.

20 . 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.