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

作者：Ishii Takayuki; Asai Tomohiro; Oyama Dai; Fukuta Tatsuya; Yasuda Nodoka; Shimizu Kosuke; Minamino Tetsuo; Oku Naoto^*

来源：Journal of Controlled Release, 2012, 160(1): 81-87.

DOI：10.1016/j.jconrel.2012.02.004

• Ischemic stroke
• Liposome
• Middle cerebral artery occlusion
• Nanoparticle
• Neuroprotection

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.

• 出版日期2012-5-30