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Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Neovascular Age-Related Macular Degeneration
Russell Simmers, Depts. of Physics and Chemistry, with Dr. Qingguo Xu, VCU School of Pharmacy
Background: Neovascular age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population in the industrialized world. The current treatment for neovascular AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy; however, nearly 40-50% of patients do not fully respond to anti-VEGF therapy. Therefore, non-VEGF therapeutics are required for neovascular AMD treatment. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist and has demonstrated robust therapeutic effects on neovascular AMD in animal models; however, it must be delivered frequently via intravitreal injection due to quick clearance of the drug from the eye, and may induce injection associated side effects such as retinal detachment, ocular hemorrhage and endophthalmitis. Purpose: To develop and optimize fenofibrate-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Feno-NP) with high-drug loading and long-lasting drug release profile to effectively treat neovascular AMD for 6-months with one single intravitreal injection. Methods: Feno-NPs were prepared by emulsification method and were fully characterized in terms of particle size, surface charge, morphology and in vitro drug release profiles and the ocular pharmacokinetics studies were performed in rats following intravitreal injection. Efficacy on neovascular-AMD was determined by measuring vascular leakage, vascular permeability, and the numbers of subretinal neovascular (SRNV) and intraretinal neovascular (IRNV) lesions after intravitreal injection of Feno-NPs in a laser-induced choroid neovascularization (CNV) rat model.
Qingguo Xu, Ph.D.
Virginia Commonwealth University. Undergraduate Research Opportunities Program
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