Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone

Abstract

The present study involved design of dexamethasone-sodium phosphate (DEX) loaded mucoadhesive chitosan nanoparticles for topical ocular delivery to improve its precorneal retention and corneal permeability. The chitosan-sodium tripolyphosphate nanoparticle (CS-NPs) was developed through ionotropic-gelation technique. The developed CS-NPs were coated with hyaluronic-acid (HA) to make discrete, free-flowing NPs and to improve their mucoadhesive characteristics. The particle-size, zeta-potential and polydispersity-index were determined by Malvern-Zetasizer. The average size of the CS-NPs ranged from 305.25 ± 14.29 nm (without HA-coating and before freeze-drying) to 400.57 ± 15.23 nm (HA-coated and after freeze-drying). Due to the polyanionic nature of HA, reversing of zeta-potentials from +32.55 ± 4.15 to -33.74 ± 3.45 was observed. Polydispersity-indices varied from 0.178 ± 0.067 (before freeze-drying of HA-coated F2) to 0.427 ± 0.028 (after freeze-drying of HA-coated F2). The encapsulation and loading capacity of around 72.95% and 14.51% respectively were found in optimized CS-NPs. In simulated tear fluid 75.84% cumulative amount of released drug was detected and the in-vitro release results suggested the mechanism of drug release was Fickian-diffusion type. The clarity, pH, refractive index, surface tension and viscosity of the suspensions of DEX-CS-NPs were found promising for ocular use. Stability study on nanoparticles revealed no significant changes were observed in particle-size, encapsulation, drug release and physicochemical characteristics at 25 °C for 3-months storage.