Topical ocular delivery of a COX-II inhibitor via biodegradable nanoparticles

Abstract

The present investigation strives to formulate nanoparticles of poly-ϵ-caprolactone (PCL), containing celecoxib (CXB), a non-steroidal anti-inflammatory agent. The CXB-PCL nanoparticles were formulated by solvent displacement method and optimized based on formulation variables like drug-to-polymer ratio and surfactant concentration. The formulations were characterized for particle dimensions, surface morphology, physicochemical features, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy against arachidonic acid-induced ocular inflammation, and stability study. The prepared nanoparticles were nearly spherical having particle sizes ranging from 89.16±8.2 nm to 191.27±12.1 nm with maximum entrapment efficiency of 97.03±0.20%. The drug release was in sustained fashion (<75% drug released after 8 h) and obeyed zero-order release kinetics. The trans-corneal permeation was significantly higher than the aqueous suspension of CXB (p=0.05). Further, % hydration level was observed within permissible ranges suggesting ocular tolerability. The anti-inflammatory activity was found better as there was observed an improvement in parameters like lid closure score, PMN counts, and protein content against CXB aqueous suspension. The formulations were stable as evident from accelerated stability testing results. Thus, the CXB-PCL nanoparticles may prove a viable alternative to conventional dosage forms offering enhanced ocular bioavailability and compatibility with ocular milieu.