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

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.

本研究旨在探究聚己内酯-聚乙二醇-聚己内酯（polycaprolactone-polyethylene glycol-polycaprolactone, PCL-PEG-PCL）胶束增强地塞米松（dexamethasone, DEX）抗炎效果的能力。采用薄膜水化法制备载地塞米松的PCL-PEG-PCL胶束。以L929细胞为模型，考察所得胶束的体外细胞毒性。通过流式细胞术（flow cytometry）与荧光显微镜法（fluorescence microscopy）研究细胞摄取行为。通过玻璃体内注射（intravitreal injection）鼠伤寒沙门氏菌（Salmonella typhimurium）内毒素，构建兔前葡萄膜炎模型。采用Hogan分类法（Hogan’s classification）对炎症诱导后的病情严重程度进行临床分级，并检测房水（aqueous humor）中的蛋白质浓度。实验结果显示，PCL-PEG-PCL胶束对L929细胞具有良好的生物相容性，且细胞摄取量呈浓度与时间依赖性。载DEX胶束可在一段滞后时间后缓解葡萄膜炎的临床症状。在脂多糖（lipopolysaccharide, LPS）注射后24小时与36小时，PCL-PEG-PCL胶束对葡萄膜炎的抑制效果优于市售滴眼液，但二者差异未达到统计学显著性水平。本研究证实，PCL-PEG-PCL胶束可作为DEX的递送载体用于治疗前葡萄膜炎，不过该研究思路仍需进一步深入探究。