Selectively Polymerizable Compositions and Methods of Use in Vivo

Abstract

Otologic materials and methods are provided. For example, a cell-adhesive, biodegradable hydrogel scaffold loaded with time-released drugs for repairing chronic tympanic membrane perforations is disclosed, methods of making same and administering same are provided. This hydrogel may promote vascular in-growth and epithelial cell growth of the tympanic membrane with the purpose of closing the perforation and providing a barrier between the external and middle ear. The hydrogel is initially a liquid polymer that only gels upon exposure to specific conditions, such as exposure to light. This scaffold may simultaneously induce repair of the tympanic membrane while preventing or alleviating middle ear infection, thus filling a void in current tympanic membrane perforation therapies.

1 . An injectable liquid composition for administration on an ear drum comprising:
 (a) methacrylated chitosan;   (b) a first polymer selected from hyaluronic acid and methacrylated hyaluronic acid;   (c) a solvent; and   (d) an initiator,   wherein prior to activation the composition has a viscosity of at least about 2800 cP, and   wherein when the initiator is activated the injectable liquid composition forms a scaffold.   
     
     
         2 . The injectable liquid composition of  claim 1 , wherein the methacrylated chitosan is 40% or more methacrylated. 
     
     
         3 . The injectable liquid composition of  claim 1 , wherein the first polymer is methacrylated hyaluronic acid and the methacrylated hyaluronic acid is at least 90% methacrylated. 
     
     
         4 . The injectable liquid composition of  claim 1 , wherein the first polymer is methacrylated hyaluronic acid and the methacrylated hyaluronic acid is at least 30% methacrylated. 
     
     
         5 . The injectable liquid composition of  claim 1 , wherein the initiator is a photoinitiator. 
     
     
         6 . The injectable liquid composition of  claim 5 , wherein the photoinitiator is 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propan-1-one; a combination of eosin Y, 1-vinyl-2-pyrrolidinone and triethanolamine; camphorquinone; and riboflavin 5′-monophosphate sodium salt. 
     
     
         7 . The injectable liquid composition of  claim 1 , wherein the initiator is 30 μM riboflavin 5′-monophosphate sodium salt as initiator 
     
     
         8 . The injectable liquid composition of  claim 1 , wherein the composition is at least 2% by weight methacrylated chitosan. 
     
     
         9 . The injectable liquid composition of  claim 1 , wherein the composition is about 4% by weight methacrylated chitosan. 
     
     
         10 . The injectable liquid composition of  claim 1 , wherein the composition is at least 1% by weight the first polymer. 
     
     
         11 . The injectable liquid composition of  claim 1 , wherein the solvent is water. 
     
     
         12 . The injectable liquid composition of  claim 11 , further comprising a therapeutic composition. 
     
     
         13 . The composition of  claim 12 , wherein the therapeutic composition is an antibiotic. 
     
     
         14 . The composition of  claim 13 , wherein the antibiotic is ciprofloxacin. 
     
     
         15 . A photo-polymerizable, injectable, otological composition comprising:
 (a) 2 wt % methacrylated chitosan;   (b) a first polymer selected from at least 1 wt % hyaluronic acid and at least 1 wt % methacrylated hyaluronic acid;   (c) 30 μM riboflavin 5′-monophosphate sodium salt as initiator; and   (d) water as solvent,   wherein the photo-polymerizable, injectable, otological composition has a viscosity of at least about 2800 cP.   
     
     
         16 . The liquid pre-polymer composition of  claim 15 , wherein the first polymer is methacrylated hyaluronic acid has a degree of methacrylation of at least about 90%. 
     
     
         17 . The liquid pre-polymer composition of  claim 15 , wherein the first polymer is methacrylated hyaluronic acid has a degree of methacrylation of at least about 30%. 
     
     
         18 . The liquid pre-polymer composition of  claim 15 , wherein the methacrylated chitosan has a degree of methacrylation of about 40%. 
     
     
         19 . The liquid pre-polymer composition of  claim 15 , comprising 4% by weight methacrylated chitosan. 
     
     
         20 . An injectable photo-polymerizable otological composition comprising:
 (a) at least 2% wt methacrylated chitosan;   (b) at least 1% wt hyaluronic acid;   (c) riboflavin 5′-monophosphate sodium salt;   (d) water; and   (e) an antibiotic,   wherein the photo-polymerizable, injectable, otological composition has a viscosity of at least about 2800 cP.