PLA–PCL–PEG–PCL–PLA based micelles for improving the ocular permeability of dexamethasone: development, characterization, and in vitro evaluation

Abstract

The aim of the present research was to investigate the feasibility of developing polylactide–polycaprolactone–polyethylene glycol–polycaprolactone–polylactide (PLA–PCL–PEG–PCL–PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA–PCL–PEG–PCL–PLA copolymers were synthesized by a ring-opening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an ex vivo bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull’s distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA–PCL–PEG–PCL–PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.