Silk Fibroin Hydrogels and Uses Thereof
The present specification provides for methods for purifying fibroins, purified fibroins, methods of conjugating biological and synthetic molecules to fibroins, fibroins conjugated to such molecules, methods of making fibroin hydrogels, fibroin hydrogels and fibroin hydrogel formulations useful for a variety of medical uses, including, without limitation uses as bulking agents, tissue space fillers, templates for tissue reconstruction or regeneration, cell culture scaffolds for tissue engineering and for disease models, surface coating to improve medical device function, or drug delivery devices.
1 . A drug delivery platform comprising a hydrogel formulation comprising:
a) a gel phase, the gel phase including hydrogel particles comprising a substantially sericin-depleted silk fibroin, an amphiphilic peptide, an a pharmaceutically-active drug; and
b) a carrier phase.
2 . The drug delivery platform of claim 1 , wherein the hydrogel particles 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.
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 particles 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 particles 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 a protein structure having a β-sheet conformation of at least 80%.
9 . The drug delivery platform of claim 1 , wherein the hydrogel particles comprises a protein structure having a β-sheet conformation of at least 50%.
10 . The drug delivery platform of claim 1 , wherein the hydrogel particles comprises a protein structure having a β-sheet conformation of at least 20%.
11 . The drug delivery platform of claim 1 , wherein the hydrogel particles comprises a protein structure having an α-helical and random coil conformation of at most 20%.
12 . The drug delivery platform of claim 1 , wherein the hydrogel particles have a cross-sectional area from about 5 μm 2 to about 1000 μm 2 .
13 . The drug delivery platform of claim 1 , wherein the hydrogel particles have a cross-sectional area from about 300 μm 2 to about 600 μm 2 .
14 . The drug delivery platform of claim 1 , wherein the carrier phase comprises saline.
15 . The drug delivery platform of claim 1 , wherein the carrier phase comprises a surfactant solution.
16 . The drug delivery platform of claim 1 wherein the gel phase is 50% to 99% of the total formulation volume, the remainder being a carrier solution.
17 . The drug delivery platform of claim 14 , wherein the gel phase is 75% of the total formulation volume, the remainder being a carrier solution.
18 . The drug delivery platform of claim 1 , wherein the platform is an extended drug release platform.
19 . The drug delivery platform of claim 18 , 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
20 . The drug delivery platform of claim 1 , wherein the platform is a sustained drug release platform.
21 . The drug delivery platform of claim 20 , 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.