title: Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin.
abstract: 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 neuroprotectant 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 24h 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 from I/R injury, and that this liposomal DDS has potential as a novel strategy for the treatment of cerebral I/R injury.
authors.affiliation: Department of Medical Biochemistry and Global COE, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishii
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Dai
authors.initials: D
authors.lastname: Oyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuta
authors.forename: Nodoka
authors.initials: N
authors.lastname: Yasuda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001212:Asialoglycoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D014018:Tissue Distribution
chemical_list: D001212:Asialoglycoproteins; D008081:Liposomes; D018696:Neuroprotective Agents; C500605:asialoerythropoietin; D004921:Erythropoietin