Silk-based drug delivery system

Abstract

The present invention provides for novel sustained release silk-based delivery systems. The invention further provides methods for producing such formulations. In general, a silk fibroin solution is combined with a therapeutic agent to form a silk fibroin article. The article is then treated in such a way as to alter its conformation. The change in conformation increases its crystallinity or liquid crystallinity, thus controlling the release of a therapeutic agent from the formulation. This can be accomplished as single material carriers or in a layer-by-layer fashion to load different therapeutic agents or different concentrations of these agents in each layer.

What is claimed is: 
     
         1 . A composition comprising at least one therapeutic agent distributed in a silk fibroin article, wherein crystallinity (beta-sheet) or liquid crystallinity of the silk fibroin article is modified to release said at least one therapeutic agent over at least about 12 hours. 
     
     
         2 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to release said at least one therapeutic agent over at least about 24 hours. 
     
     
         3 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to release said at least one therapeutic agent over a period of about 2 to 90 days. 
     
     
         4 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to release said at least one therapeutic agent over a period of about 3 to 60 days. 
     
     
         5 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to release said at least one therapeutic agent over a period of about 3 to 10 days. 
     
     
         6 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to reduce initial burst of said at least one therapeutic agent. 
     
     
         7 . The composition of  claim 1 , wherein the crystallinity (beta-sheet) of the silk fibroin article is modified to release said at least one therapeutic agent in an amount of about 1 ng/day to about 1 mg/day. 
     
     
         8 . The composition of  claim 1 , wherein the release of said at least one therapeutic agent is sustained over the period of time. 
     
     
         9 . The composition of  claim 1 , wherein said at least one therapeutic agent is equal to or greater than 10 kilodaltons. 
     
     
         10 . The composition of  claim 9 , wherein said at least one therapeutic agent is selected from the group consisting of a protein, a peptide, nucleic acid, PNA, aptamer, antibody, small molecule, and any combinations thereof. 
     
     
         11 . The composition of  claim 1 , wherein the silk fibroin article is selected from the group consisting of a thread, fiber, foam, mesh, hydrogel, three-dimensional scaffold, tablet filling material, tablet coating, microsphere, and any combinations thereof. 
     
     
         12 . The composition of  claim 1 , wherein the silk fibroin article is biodegradable. 
     
     
         13 . The composition of  claim 1 , wherein the silk fibroin article further comprises a biocompatible polymer. 
     
     
         14 . The composition of  claim 1 , wherein the silk fibroin article comprises at least two layers, said at least one layer having crystallinity or liquid crystallinity different from that of at least one other layer. 
     
     
         15 . The composition of  claim 14 , further comprising a targeting agent that specifically targets the device to a specific cell or tissue type. 
     
     
         16 . A method comprising:
 i. forming a silk fibroin article comprising a therapeutic agent; and   ii. contacting said article with water vapor at a pre-determined temperature, thereby inducing crystallinity of the silk fibroin to modify release of said therapeutic agent from said article.   
     
     
         17 . The method of  claim 16 , wherein the crystallinity of the silk fibroin is induced by water vapor to modify release of said therapeutic agent from said article over at least about 12 hours. 
     
     
         18 . The method of  claim 16 , wherein the crystallinity of the silk fibroin is induced by water vapor to modify release of said therapeutic agent from said article over at least about 24 hours. 
     
     
         19 . The method of  claim 16 , wherein the crystallinity of the silk fibroin is induced by water vapor to modify release of said therapeutic agent from said article over a period of about 2 to 90 days. 
     
     
         20 . The method of  claim 16 , wherein the pre-determined temperature is about 25° C. 
     
     
         21 . The method of  claim 16 , further comprising subjecting said article to a shear stress, an electric field, pressure, salt, or any combinations thereof. 
     
     
         22 . The method of  claim 16 , wherein the silk fibroin article comprises a film.