Evaluation of anti-inflammatory impact of dexamethasone-loaded PCL-PEG-PCL micelles on endotoxin-induced uveitis in rabbits.
Mitra JelvehgariParvin Zakeri-MilaniHadi ValizadehShahram SattariSara SalatinMitra JelvehgariPublished in: Pharmaceutical development and technology (2019)
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.
Keyphrases
- drug delivery
- cancer therapy
- drug release
- induced apoptosis
- juvenile idiopathic arthritis
- anti inflammatory
- ankylosing spondylitis
- cell cycle arrest
- high glucose
- diabetic rats
- oxidative stress
- low dose
- drug induced
- high dose
- escherichia coli
- machine learning
- endoplasmic reticulum stress
- single molecule
- rheumatoid arthritis
- high resolution
- small molecule
- disease activity
- depressive symptoms
- climate change
- optical coherence tomography