Sunitinib formulations and methods for use thereof in treatment of glaucoma

Abstract

Methods for increasing the encapsulation or incorporation of Sunitinib into polymeric matrices have been developed. The resulting formulations provide for more sustained controlled release of sunitinib or other inhibitors of JNK signaling, which bind to DLK. Increased loading is achieved using an alkaline solvent system. The pharmaceutical compositions can be administered to treat or reduce neuronal death due to elevated intraocular pressure. Upon administration, the sunitinib or other inhibitor is released over an extended period of time at concentrations which are high enough to produce therapeutic benefit, but low enough to avoid unacceptable levels of cytotoxicity, and which provide much longer release than inhibitor without conjugate.

1 - 9 . (canceled) 
     
     
         10 . A composition for administration to the eye comprising polymeric microparticles with increased sunitinib encapsulation having an average diameter between one and 50 microns comprising sunitinib or a pharmaceutically acceptable salt thereof encapsulated in a blend of poly(lactide-co-glycolide) (PLGA) and poly(lactide-co-glycolide) (PLGA) conjugated to polyethylene glycol (PEG), wherein the polymeric microparticles release the sunitinib for at least two weeks and wherein the polymeric microparticles comprise greater than 5% sunitinib. 
     
     
         11 . The composition of  claim 10 , wherein the microparticles further comprise PLA. 
     
     
         12 . The composition of  claim 10 , wherein the pharmaceutically acceptable salt is sunitinib malate. 
     
     
         13 . The composition of  claim 10 , wherein the average diameter of the microparticles is between one and 30 microns. 
     
     
         14 . The composition of  claim 10 , wherein the polymeric microparticles are administered via intravitreal injection. 
     
     
         15 . The composition of  claim 10 , wherein the polymeric microparticles are administered via subconjunctival injection. 
     
     
         16 . The composition of  claim 10 , wherein the polymeric microparticles comprise greater than 10% sunitinib. 
     
     
         17 . The composition of  claim 10 , wherein the polymeric microparticles comprise greater than 15% sunitinib.