DEVELOPMENT OF DEXAMETHASONE SODIUM PHOSPHATE –LOADED POLYMERIC NANOPARTICLES AS A DELIVERY SYSTEM FOR THE ANTERIOR SEGMENT OF THE EYE

Abstract

Objective: Uveitis is an inflammatory ocular disease that requires localized and sustained corticosteroid delivery to minimize systemic exposure and adverse effects. Conventional dexamethasone formulations are limited by poor corneal penetration,     rapid precorneal clearance, and the need for frequent administration. This study aims to develop and optimize dexamethasone sodium phosphate (DSP)–loaded polymeric nanoparticles (NPs) for anterior segment ocular delivery using ionotropic gelation with chitosan and different polyanionic crosslinkers (sodium alginate, tripolyphosphate (TPP), and hyaluronic acid (HA).

Methods: Dexamethasone sodium phosphate–loaded nanoparticles based on chitosan–TPP, chitosan–hyaluronic acid, and chitosan–sodium alginate were prepared by ionotropic gelation. A Box–Behnken design was applied to optimize the nanoparticle formulation. Drug content and in vitro release were quantified by HPLC according to the USP monograph for dexamethasone sodium phosphate. Nanoparticles were characterized by particle size, polydispersity index, and zeta potential using a Malvern Zeta-sizer, while morphology was examined by TEM. X-ray diffraction evaluated crystallinity or amorphous nature, and FTIR analyzed functional groups and potential drug–polymer interactions. In vitro drug release was studied using the dialysis bag method in simulated tear fluid (pH 7.4).Ex vivo corneal permeation studies were conducted to determine steady-state flux (Jss) and permeability coefficient.

Results: Dexamethasone sodium phosphate–sodium alginate–chitosan nanoparticles had a particle size of 496 nm with a PDI of 0.408, a zeta potential of +26 mV, and a drug content of 1.1 mg (112%), while the optimized dexamethasone sodium phosphate–TPP–chitosan nanoparticles had a particle size of 480 nm with a PDI of 0.150, a zeta potential of +29 mV, and a drug content of 1.1 mg/mL (115%). Dexamethasone sodium phosphate–hyaluronic acid–chitosan nanoparticles had a particle size of 366 nm with a PDI of 0.217, a zeta potential of +18 mV, and a drug content of 1.2 mg/ml. All formulations exhibited sustained drug release over 24 h. The steady-state flux values were 0.089, 0.080, and 0.074 mg/cm²·h⁻¹ for chitosan–TPP, hyaluronic acid–chitosan, and sodium alginate–chitosan nanoparticles, respectively, with corresponding permeability coefficients of 0.078, 0.067, and 0.066 cm/h. FTIR and XRD confirmed that the drug–polymer interactions and amorphous entrapment, while TEM revealed spherical morphology.

Conclusion: Dexamethasone sodium phosphate-loaded chitosan-based nanoparticles exhibited release over 24h.This reduced the dosing frequency for dexamethasone sodium phosphate and improved corneal penetration and bioavailability in the anterior segment of the eye.