Nanoparticle-integrin antagonist C16Y peptide treatment of choroidal neovascularization in rats

作者：Kim Hyuncheol^*; Csaky Karl G

来源：Journal of Controlled Release, 2010, 142(2): 286-293.

DOI：10.1016/j.jconrel.2009.10.031

• Choroidal neovascularization
• Nanoparticles
• Integrin antagonist
• Intravitreal injection

Choroidal neovascularization (CNV) is the major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present drug delivery may be limited by poor delivery to the choroid where CNV originates. The goal of this study was to develop a drug delivery system to deliver an integrin-antagonist peptide to the sub-retinal space. We developed polylactic acid/polylactic acid-polyethylene oxide nanoparticles (PLA/PLA-PEO) encapsulating the water-soluble integrin-antagonist pepticle, C16Y (C16Y-NP). The PLA/PLA-PEO nanoparticles were 302 +/- 85.1 nm in size and demonstrated a two-week sustained release, in vitro, of encapsulated C16Y. Injected nanoparticles did not demonstrate retinal toxicity as determined by histopathology. C16Y pepticle solution or C16Y-NP was injected 5 or 9 days post laser photocoagulation. A single intravitreal injection of C16Y pepticle and C16Y-NP solution at both 5 days and 9 days post laser photocoagulation statistically inhibited CNV (p<0.05). However, for the day 5 injections the area of choroidal neovascularization on day 12 was smaller for C16Y-NP than for C16Y pepticle solution (p<0.05) because of the short vitreous half-life of C16Y pepticle solution. These results demonstrate the importance of sustained release delivery for the treatment of choroidal neovascularization associated with age-related macular degeneration. The intravitreally administered PLA/PLA-PEO containing coumarin was found to penetrate the retina and localize to the RPE. These results suggest that nanoparticles of biodegradable polymers may be a potential useful delivery system for intravitreal injection of drugs in the treatment of AMD.

• 出版日期2010-3-3