title: A single injection of liposomal asialo-erythropoietin improves motor function deficit caused by cerebral ischemia/reperfusion.
abstract: Modification of the liposomal surface with a targeting molecule is a promising approach for the targeted delivery of therapeutics. Asialo-erythropoietin (AEPO) is a potent tool for targeting an ischemic region by binding to the EPO receptors on neuronal cells. Additionally, it shows a strong cytoprotective effect against programed cell death. Hence, AEPO-modified liposomes appear likely to have both a neuronal-targeting character and a neuroprotective effect on cerebral ischemic injury. In this study, we assessed the targeting ability of AEPO-modified PEGylated liposomes (AEPO-liposomes) to ischemic region and their improvement effect on neurological deficits induced by ischemia/reperfusion (I/R) in transient middle cerebral artery occlusion (t-MCAO) rats. Immunohistological analysis showed that the AEPO-liposomes given immediately after reperfusion extravasated into the ischemic region and attached strongly to neuronal cells. Also, neuronal nuclei (NeuN) staining was clearly visible only in the AEPO-liposome-treated group, suggesting that AEPO-liposomes protected neuronal cells from ischemia/reperfusion-induced damage. Moreover, a single administration of low-dose AEPO-liposomes significantly improved the neurological deficit compared to vehicle and free-AEPO treatment at 7 days after injection. In conclusion, AEPO-liposomes have clear potential as a neuroprotectant after stroke and as a DDS device targeting ischemic regions.
authors.affiliation: Department of Medical Biochemistry and Global COE, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishii
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuta
authors.forename: Dai
authors.initials: D
authors.lastname: Oyama
authors.forename: Nodoka
authors.initials: N
authors.lastname: Yasuda
authors.forename: Yurika
authors.initials: Y
authors.lastname: Agato
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; D001212:Asialoglycoproteins / Q000008:administration & dosage*; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D008081:Liposomes; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D001212:Asialoglycoproteins; D008081:Liposomes; D018696:Neuroprotective Agents; C500605:asialoerythropoietin; D004921:Erythropoietin; D011092:Polyethylene Glycols