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

被引:35
作者
Alami-Milani, Mitra [1 ,2 ]
Zakeri-Milani, Parvin [3 ,4 ]
Valizadeh, Hadi [1 ,4 ]
Sattari, Shahram [5 ]
Salatin, Sara [2 ,6 ]
Jelvehgari, Mitra [1 ,4 ]
机构
[1] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran
[2] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran
[3] Tabriz Univ Med Sci, Liver & Gastrointestinal Dis Res Ctr, Tabriz, Iran
[4] Tabriz Univ Med Sci, Dept Pharmaceut, Fac Pharm, Tabriz, Iran
[5] Tabriz Univ Med Sci, Nikookari Ophthalmol Ctr, Tabriz, Iran
[6] Tabriz Univ Med Sci, Res Ctr Pharmaceut Nanotechnol, Tabriz, Iran
关键词
Dexamethasone; PCL-PEG-PCL micelles; ocular drug delivery; endotoxin-induced uveitis; cellular uptake; NITRIC-OXIDE SYNTHASE; OCULAR DRUG-DELIVERY; IN-VIVO EVALUATION; PHYSICOCHEMICAL CHARACTERIZATION; SUSTAINED-RELEASE; NANOPARTICLES; VITRO; INHIBITOR; NANOCARRIERS; NANOEMULSION;
D O I
10.1080/10837450.2019.1578370
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:680 / 688
页数:9
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