Hydrogel drug delivery systems for the treatment of pediatric growth plate injuries

Abstract

The present invention relates to the unexpected discovery of compositions and methods for the treatment of growth plate defects. In certain embodiments, the methods prevent the growth of “bony bars” at the site of growth plate injury, thereby preventing growth arrest and/or deformity. In certain embodiments, the compositions comprise hydrogels comprising at least one biological factor capable of preventing bony bar formation.

1 . A gel based composition comprising at least one hydrogel polymer material selected from the group consisting of chitosan and alginate; and at least one biological factor selected from the group consisting of anti-VEGF compounds, stem cell attracting factors, and transforming growth factor beta cytokines, wherein the gel is suitable for treatment of growth plate injuries. 
     
     
         2 . The composition of  claim 1 , wherein the at least one biological factor is selected from the group consisting of SDF-1α, CCL25, TGF-β1, TGF-β3, ranibizumab, bevacizumab, lapatinib, sunitinib, sorafenib, axitinib, and pazopanib. 
     
     
         3 . The composition of  claim 1 , wherein the at least one biological factor is a monoclonal antibody raised against VEGF. 
     
     
         4 . The composition of  claim 1 , which comprises a hydrogel polyelectrolyte complex (PEC) comprising chitosan and alginate, wherein the at least one biological factor is embedded within the hydrogel PEC. 
     
     
         5 . The composition of  claim 1 , which comprises a microgel comprising chitosan, wherein the at least one biological factor is embedded within the microgel. 
     
     
         6 . The composition of  claim 5 , wherein the microgel is nested within a hydrogel comprising alginate. 
     
     
         7 . The composition of  claim 6 , wherein the hydrogel comprising alginate comprises at least one biological factor. 
     
     
         8 . The composition of  claim 7 , wherein the at least one biological factor embedded within the microgel is different from the at least one biological factor within the hydrogel. 
     
     
         9 . The composition of  claim 7 , wherein the at least one biological factor within the hydrogel is released into a surrounding environment at a higher rate than the at least one biological factor within the microgel. 
     
     
         10 . The composition of  claim 5 , wherein the chitosan is cross-linked with genipin. 
     
     
         11 . The composition of  claim 1 , wherein the composition further comprises hyaluronic acid. 
     
     
         12 . A method of treating a growth plate injury in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a hydrogel composition comprising at least one hydrogel polymer material selected from the group consisting of chitosan and alginate; at least one biological factor selected from the group consisting of anti-VEGF compounds, stem cell attracting factors, and transforming growth factor beta cytokines; and optionally hyaluronic acid. 
     
     
         13 . The method of  claim 12 , wherein the hydrogel composition is administered via injection. 
     
     
         14 . The method of  claim 13 , wherein the hydrogel composition is administered via direct injection to the growth plate injury. 
     
     
         15 . The method of  claim 12 , wherein, before the administering, a bony bar is surgically removed from the growth plate injury in the subject. 
     
     
         16 . The method of  claim 12 , which prevents the growth of bony bars in the cartilage tissue at the site of the growth plate injury. 
     
     
         17 . The method of  claim 12 , which treats or prevents at least one of the following: arrest of bone growth at the site of growth plate injury, bone deformities at the site of the growth plate injury. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 12 , wherein the subject is a mammal. 
     
     
         20 . The method of  claim 19 , wherein the subject is a human. 
     
     
         21 . The method of  claim 12 , wherein the subject is an infant, toddler, child, juvenile, adolescent or young adult.