title: Nanoparticle-integrin antagonist C16Y peptide treatment of choroidal neovascularization in rats.
abstract: 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 peptide, 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 peptide solution or C16Y-NP was injected 5 or 9 days post laser photocoagulation. A single intravitreal injection of C16Y peptide 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 peptide solution (p<0.05) because of the short vitreous half-life of C16Y peptide 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.
authors.affiliation: Chemical and Biomolecular Engineering, Sogang University, #1 Shinsu-dong Mapo-gu, Seoul 121-742, Republic of Korea. hyuncheol@sogang.ac.kr
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D005451:Fluorescein Angiography; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors*; D019344:Lactic Acid / Q000737:chemistry; D008268:Macular Degeneration / Q000188:drug therapy; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000473:pathology
chemical_list: D016023:Integrins; D010455:Peptides; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)