Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin
Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin
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DOI：
10.1016/j.jconrel.2012.02.004
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发表时间：
2012-05-30
影响因子：
10.8
通讯作者：
Oku, Naoto
中科院分区：
文献类型：
--
作者：
Ishii, Takayuki;Asai, Tomohiro;Oku, Naoto
脑缺血再灌注（I/R）损伤可导致继发性脑损伤。由于治疗这种类型损伤的药物在临床试验中表现出较差的疗效和不良副作用，因此人们期待已久的新治疗策略。在这项研究中，我们专注于脑卒中后血脑屏障的破坏，并应用脂质体给药系统（DDS），旨在提高神经保护剂的药理作用，并避免副作用。在短暂性大脑中动脉闭塞（t-MCAO）模型大鼠中，在再灌注开始后的不同时间注射PEG化脂质体。结果显示，PEG化脂质体在再灌注后早期在缺血半球积聚，并且在注射后至少24 h保留在损伤中。我们还研究了无唾液酸促红细胞生成素（AEPO）修饰的聚乙二醇化脂质体（AEPO-脂质体）治疗脑I/R损伤的有效性。与载体和AEPO治疗相比，AEPO-脂质体治疗显著减少脑I/R损伤后TTC定义的脑军团，并改善运动功能。总之，这些结果表明AEPO-脂质体是一种有前途的脂质体制剂，用于保护脑I/R损伤，并且这种脂质体DDS具有作为治疗脑I/R损伤的新策略的潜力。(C)2012年爱思唯尔B。V.保留所有权利。
Cerebral ischemia-reperfusion (I/R) injury induces secondary cerebral damage. As drugs for treating this type of injury have shown poor efficacy and adverse side effects in clinical trials, a novel therapeutic strategy has been long awaited. In this study, we focused on the disruption of the blood-brain barrier after stroke, and applied a liposomal drug delivery system (DDS) designed to enhance the pharmacological effect of the neuro-protectant and to avoid side effects. PEGylated liposomes were injected at varying time after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) model rats. The results showed PEGylated liposomes accumulated in the ischemic hemisphere at an early stage after reperfusion and were retained in the lesion for at least 24 h after injection. We also investigated the effectiveness of asialo-erythropoietin (AEPO)-modified PEGylated liposomes (AEPO-liposomes) in treating the cerebral I/R injury. AEPO-liposome treatment significantly reduced TTC-defined cerebral legion following cerebral I/R injury, and ameliorated motor function compared with vehicle and AEPO treatment. In conclusion, these results indicate that AEPO-liposomes are a promising liposomal formulation for protecting the brain fromI/R injury, and that this liposomal DDS has potential as a novel strategy for the treatment of cerebral I/R injury. (C) 2012 Elsevier B. V. All rights reserved.