Study on fabrication of mucoadhesive nanoparticles for topical delivery of dexamethasone to the eye

Abstract

Topical ocular drug delivery is limited by low drug bioavailability due to rapid clearance of the drug from the preocular surface by tear fluid or blinking. The purpose of this study is to investigate the fabrication conditions of mucoadhesive nanoparticles for topical dexamethasone delivery to the eye. Dexamethasone is a highly potent and widely used anti-inflammatory corticosteroid in ophthalmology. Nanoparticles made of biodegradable polymers have drawn a great deal of interest as drug delivery carriers. In order to resolve the topical ocular drug delivery challenge, I sought to fabricate the hydrophobic dexamethasone loaded nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) as a core material for sustained drug delivery and poly(ethylene glycol) (PEG, MW = 6000) as a mucoadhesion promoter. The nanoparticles were prepared via the single oil-in-water emulsion method and were fabricated by varying the initial feeding amounts of dexamethasone and PEG. Among the fabricated nanoparticles, the most suitable nanoparticle for the topical dexamethasone delivery to the eye was fabricated with the actual drug and PEG loading amounts of 105.7 ± 2.4 and 9.8 ± 1.0 μg/mg, respectively, and demonstrated the sustained in vitro drug release of 90.0 ± 2.7 % for 24 hours with an initial burst release of 20.8 ± 3.3 % in the first hour. Furthermore, the in vitro evaluation of the mucoadhesion study of the optimized nanoparticle with mucin confirmed the better adsorption of the nanoparticle to the mucin when compared to the nanoparticle without PEG. Also, the in vivo pharmacokinetics study demonstrated the enhanced ocular dexamethasone bioavailability with increased concentration of the absorbed dexamethasone into the aqueous humor of rabbit eyes.