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: Hyuncheol Kim, Karl G Csaky
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 142 Issue 2 Pg. 286-93 (Mar 03 2010) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 19895863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier B.V. All rights reserved.

Chemical References

• Integrins
• Peptides
• Polyesters
• Polymers
• Lactic Acid
• Polyethylene Glycols
• poly(lactide)

Topics

• Animals
• Choroidal Neovascularization (drug therapy, pathology)
• Fluorescein Angiography
• Humans
• Integrins (antagonists & inhibitors)
• Lactic Acid (chemistry)
• Macular Degeneration (drug therapy)
• Male
• Nanoparticles (chemistry)
• Peptides (administration & dosage, therapeutic use)
• Polyesters
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Rats
• Retina (drug effects, pathology)