Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone
Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone
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DOI：
10.1016/j.exer.2009.03.012
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发表时间：
2009-08-01
影响因子：
3.4
通讯作者：
Calonge, Margarita
中科院分区：
文献类型：
--
作者：
Barcia, Emilia;Herrero-Vanrell, Rocio;Calonge, Margarita
我们测试了聚乳酸-乙醇酸(PLGA)微球负载地塞米松对兔玻璃体内注射脂多糖(LPS)引起的眼部炎症的短期和长期的影响。以油/水乳状液为原料，采用溶剂挥发法制备了地塞米松PLGA微球，并对其进行了辐照灭菌。选择的微球比例为2：10(地塞米松：PLGA)，含141+/-0.38mg地塞米松/mg PLGA。微球直径为20~53微米，平均包封率为92.97+/-0.75%。在诱导全葡萄膜炎前7天，玻璃体内注入10 mg不含地塞米松或含地塞米松的微球。对照组动物没有接受任何注射。雄性新西兰大白兔(2.5~3.0 kg)玻璃体腔注射大肠杆菌脂多糖诱发全葡萄膜炎。在15天的短期研究和33天的长期研究中，进行了临床评估、视网膜电图和组织病理学研究。在玻璃体切除的眼睛中也研究了减少炎症的效果。在短期研究中，注射地塞米松微球的眼睛比对照组和注射空白微球的眼睛炎症更轻。注射内毒素后15d，各组炎症反应均恢复正常。在第30天给予第二次唇部注射，在对照组和注射空白微球的眼睛中引发了炎症的高峰期。相比之下，注射地塞米松微球的眼睛只出现轻微炎症。组织病理学和微电图术支持这些结果。在短期和长期研究中，地塞米松微球有效地减少了由内毒素引起的眼内炎症。(C)2009爱思唯尔有限公司。保留所有权利。
We tested the short- and long-term ability of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone to reduce ocular inflammation in rabbits elicited by intravitreal lipopolysaccharide (LPS) injection. PLGA microspheres loaded with dexamethasone were prepared by the solvent evaporation technique from an oil/water emulsion and sterilized by gamma irradiation (25 kGy). The microsphere fraction selected was 2:10 (dexamethasone:PLGA) and contained 141 +/- 0.38 mu g dexamethasone/mg PLGA. Microsphere diameters were 20-53 mu m, and the mean encapsulation efficiency was 92.97 +/- 0.75%. Seven days prior to the induction of panuveitis, 10 mg of dexamethasone-free or dexamethasone-loaded microspheres were injected into the vitreous. Control animals received no injection. Panuveitis was induced in male New Zealand rabbits (2.5-3.0 kg) by intravitreal injection of Escherichia coli LPS. Clinical evaluation, electroretinography and histopathologic studies were performed in short-term studies of 15 days and in long-term studies of 33 days. Efficacy in reducing inflammation was also studied in vitrectomized eyes. In short-term studies eyes injected with dexamethasone-loaded microspheres had less inflammation than control eyes and eyes injected with blank microspheres. Inflammation reverted in all groups by 15 days after LPS injection. A second LIPS dose given on Day 30 provoked a high peak of inflammation in control eyes and in those injected with blank microspheres. In contrast, only slight inflammation occurred in eyes injected with dexamethasone-loaded microspheres. Histopathology and electrorefinography supported these results. Dexamethasone-loaded microspheres effectively reduced intraocular inflammation caused by LPS in both short- and long-term studies. (C) 2009 Elsevier Ltd. All rights reserved.