482c Integrin Antagonist C16y Peptide Encapsulating Pla & Pla-Peo Nanoparticle Treatment of Choroidal Neovascularization in Rodents

Hyuncheol Kim, Michelle Thill, Lourdes Ponce, Nufayl Khan, and Karl G. Csaky. National Eye Institute, National Institutes of Health, Bldg 10/Rm 10B11, 9000 Rockville Pk, Bethesda, MD 20892

Choroidal neovascularization (CNV) is the major cause of severe vision loss in patients with age-related macular degeneration (AMD) and to date pharmacotherapy appears to offer the best therapy. However, delivery to the outer retina and choroid may limit present therapy. Herein, we developed water-soluble integrin-antagonist peptide, C16Y, encapsulating nanoparticles by blending polylactic acid and polylactic acid - polyethylene oxide. We evaluated the nanoparticles with a rodent laser model of CNV. The developed nanoparticles showed 302 +/- 85.1 nm size and two-weeks sustained release of encapsulated C16Y. The nanoparticles did not show any toxicity in the retina. C16Y solution or C16Y encapsulating nanoparticles were injected 5 days or 9 days post laser photocoagulation. Intravitreal injection of C16Y solution 9 days post laser photocoagulation inhibited CNV compared to the control (p < 0.01) while treatment at 5 days post laser photocoagulation did not (p = 0.05). Intravitreal injection of C16Y encapsulating nanoparticles both 5 days and 9 days post laser photocoagulation inhibited the CNV successfully, respectively (p < 0.01). These results suggest that nanoparticles of biodegradable polymers may be a potential delivery system for the sustained release of drugs in the vitreous in the treatment of age-related macular degeneration.