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学科主题: 临床医学
题名:
Therapeutic and toxicological evaluations of cyclosporine a microspheres as a treatment vehicle for uveitis in rabbits
作者: He, Y; Wang, JC; Liu, YL; Ma, ZZ; Zhu, XA; Zhang, Q
刊名: JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
发表日期: 2006-04-01
卷: 22, 期:2, 页:121-131
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Ophthalmology ; Pharmacology & Pharmacy
研究领域[WOS]: Ophthalmology ; Pharmacology & Pharmacy
关键词[WOS]: ENDOTOXIN-INDUCED UVEITIS ; SUSTAINED-RELEASE CYCLOSPORINE ; INTRAVITREAL CYCLOSPORINE ; DELIVERY DEVICE ; RATS ; DEXAMETHASONE ; TOXICITY ; SAFETY
英文摘要:

Aim: This study was undertaken to investigate the therapeutic efficacy and the toxicity of the intravitreal biodegradable poly(dl-lactide-co-glycolide)co-polymer microspheres containing cyclosporin A (CsA-PLGA-MS) on experimental uveitis in rabbits.

Methods: CsA-PLGA-MS that had been prepared by a solvent evaporation approach were characterized for morphology, particle size, entrapment efficiency, and in vitro release profile of CsA-PLGA-MS. Therapeutic efficacy of the CsA-PLGA-MS was evaluated by scoring of the inflammation; aqueous leukocyte counting, aqueous protein determination, and histological examination in the experimental rabbits with artificial uveitis induced by the injection of lipopolysaccharide. The toxicity was investigated by slit-lamp examination, indirect ophthalmoscopy, and electroretinography (ERG) in the noninflamed rabbit eye.

Results: The CsA-PLGA-MS were spherical in shape, with an average particle size of nearly 50 mu m and an entrapment efficiency of more than 80%. The compositions of the formulation that was most effective in the in vivo studies included CsA, PLGA, and 3% Pluronic F68. In vitro released cyclosporine A from the optimized microspheres was approximately 25% during the 60-day incubation at 37 degrees C. It was demonstrated that the intravitreal injection of the optimized CsA-PLGA-MS decreased significantly the severity of the inflammatory signs, cellular infiltrate, aqueous leukocyte counts, and protein levels in the eyes of experimental rabbits with uveitis, compared to other formulations. Also, the preparation did not cause obvious toxicity in the noninflamed eyes of rabbits, except that the ERG b-wave amplitude for the test eyes was reversibly depressed, compared to those of the control eyes at 2 weeks, which almost recovered at the end of 6 weeks.

Conclusions: The CsA-PLGA-MS preparation might be useful in the treatment of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.

语种: 英语
WOS记录号: WOS:000237401700006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68135
Appears in Collections:北京大学第三临床医学院_眼科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Dept Ophthalmol, Beijing 100871, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China

Recommended Citation:
He, Y,Wang, JC,Liu, YL,et al. Therapeutic and toxicological evaluations of cyclosporine a microspheres as a treatment vehicle for uveitis in rabbits[J]. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS,2006,22(2):121-131.
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