(644c) Subconjunctivally Administrated Hydrogels/Nanogels for Treating Diabetic Retinopathy

Diabetic retinopathy remains a major cause of vision impairment and no treatments are available that can be applied locally to the eye to prevent or treat retinopathy before loss of vision. In this talk, we will discuss our collaborative research in development of novel hydrogels/nanogels that can be subconjunctivally implanted/injected to deliver therapeutic agents to the retina to treat diabetic retinopathy and other posterior retinal diseases. The hydrogels/nanogels are thermoresponsive and hydrolytically degradable and can load drugs with high loading efficiency during the UV polymerization process. They can continuously release drug such as FITC-insulin in PBS (pH=7.4) buffer at 37 ?aC for up to 10 months in vitro depending on the composition and geometry of the hydrogels/nanogels and the drug type. Humalog released from the hydrogels is biologically active by increasing Akt phosphorylation, insulin receptor tyrosine phosphorylation, and insulin like growth factor I receptor tyrosine phosphorylation of ex vivo retinas.Subconjuctivally implanted hydrogels are well tolerated by rats for 6 weeks and can release humalog to the retina to reduce the DNA fragmentation of the retinas of diabetic rats after one week implantation. Furthermore, the developed nanogels are highly permeable across the ex vivo porcine sclera/choroid/RPE barrier(s) and reach to the retina after subconjunctival injection in rats.