Evaluation of anti-inflammatory impact of dexamethasone-loaded PCL-PEG-PCL micelles on endotoxin-induced uveitis in rabbits

Abstract

The aim of this study was to investigate the capability of polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles in improving the anti-inflammatory effects of dexamethasone (DEX). A film hydration method was used for the preparation of the DEX-loaded PCL-PEG-PCL micelles. In vitro cytotoxicity of the micelles obtained was investigated on L929 cells. Cellular uptake was studied by using flow cytometry and fluorescence microscopy. Anterior uveitis was induced in a group of rabbits by intravitreal injection of endotoxin from Salmonella typhimurium. The severity of inflammation-induced was clinically graded by using Hogan’s classification method. Protein concentration in the aqueous humor was also measured. The micelles exhibited suitable compatibility on L929 cells and were taken up by the cells in a concentration- and time-dependent manner. The DEX-loaded micelles could reduce the clinical symptoms of uveitis after a lag-time. At 24 and 36 h after the LPS injection, the PCL-PEG-PCL micelles showed a better inhibitory effect on uveitis than the marketed eye drop, the differences did not reach significant levels though. This study demonstrated the potential of the PCL-PEG-PCL micelles as carriers for DEX in treating anterior uveitis. However, this concept is still to be further investigated.

Keywords:

• Dexamethasone
• PCL-PEG-PCL micelles
• ocular drug delivery
• endotoxin-induced uveitis
• cellular uptake

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors want to thank the authorities of the Research Council of Tabriz University of Medical Sciences for their financial support. The Student Research Center is also greatly acknowledged for a partial grant-in-aid (No. 61542). This article was written based on a dataset of a PhD thesis (No. 111) registered at Tabriz University of Medical Sciences, Tabriz, Iran.