Abstract
In several ocular diseases, the vascular endothelial growth factor (VEGF) level has been found to be upregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for these conditions. Delivery of drug to the posterior site is desired for the effective management of these diseases. The present study was to develop and optimize the chitosan (CS)-coated poly(lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) of bevacizumab for sustained and effective delivery to posterior ocular tissues. NPs were prepared by double emulsion solvent evaporation method and optimized for various variables (i.e., CS concentration, PLGA content, polyvinyl alcohol (PVA) concentration, and sonication time) by employing a 4-factor 3-level Box–Behnken statistical design. NPs were characterized for particle size, polydispersity index (PDI), entrapment efficiency (EE), and in vitro release. Transscleral flux was determined through goat sclera, and ocular tolerance assay was done by Hen’s Egg Test chorioallantoic membrane method. The particle size and PDI of the optimized NPs were 222.28 ± 7.45 nm and 0.19 ± 0.08, respectively. The developed NPs showed an EE of 69.26 ± 1.31% with an extended release profile. The flux was significantly higher that is, 0.3204 ± 0.026 μg/cm2/h for the NPs compared to drug solution. Thus, CS-coated PLGA NPs can be potentially useful as ocular drug carriers to target retina.
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