Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin

被引：88

作者：

Ishii, Takayuki ^{[1
,2
,3
]}

Asai, Tomohiro ^{[1
,2
]}

Oyama, Dai ^{[1
,2
]}

Fukuta, Tatsuya ^{[1
,2
]}

Yasuda, Nodoka ^{[1
,2
]}

Shimizu, Kosuke ^{[1
,2
]}

Minamino, Tetsuo ^{[4
]}

Oku, Naoto ^{[1
,2
]}

机构：

[1] Univ Shizuoka, Sch Pharmaceut Sci, Dept Med Biochem, Suruga Ku, Shizuoka 4228526, Japan

[2] Univ Shizuoka, Sch Pharmaceut Sci, Global COE, Suruga Ku, Shizuoka 4228526, Japan

[3] JSPS, Chiyoda Ku, Tokyo 1028472, Japan

[4] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan

来源：

JOURNAL OF CONTROLLED RELEASE | 2012年 / 160卷 / 01期

基金：

日本学术振兴会;

关键词：

Ischemic stroke; Liposome; Middle cerebral artery occlusion; Nanoparticle; Neuroprotection; BLOOD-BRAIN-BARRIER; FOCAL ISCHEMIA; ANIMAL-MODELS; DISRUPTION; RECEPTOR; ASIALOERYTHROPOIETIN; NEUROPROTECTION; PERMEABILITY; EXPRESSION; CANCER;

D O I：

10.1016/j.jconrel.2012.02.004

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：81 / 87

页数：7

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