title: Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced.
abstract: The use of a liposomal drug delivery system is a promising strategy for avoiding side effects and enhancing drug efficiency by changing the distribution of the intact drug. We have previously shown that liposomal agents quickly accumulated in an ischemia-reperfusion region and ameliorated cerebral ischemia-reperfusion injury when they were injected after reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. In the present study, we hypothesized that liposomes also act effectively as a drug carrier in the ischemic state, since the integrity of the blood brain barrier is disrupted at an early stage after an ischemic event. To test this hypothesis, the cerebral distribution of fluorescence-labeled liposomes was observed in permanent MCAO (p-MCAO) rats. The liposomes accumulated in the ischemic core and the penumbra region when injected at 1 or 2h after occlusion. The accumulation in the ischemic core region was clearly greater than that in the penumbra region, despite the cerebral blood perfusion of the core region being substantially reduced. This result suggests that drug delivery to an ischemic region using liposomes is possible even when cerebral blood circulation has not recovered. Because liposomal drug delivery systems have the potential to effectively employ a number of agents that have failed in clinical trials, they may offer an effective strategy for achieving neuroprotection in stroke patients.
authors.affiliation: Department of Medical Biochemistry, 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: Tatsuya
authors.initials: T
authors.lastname: Fukuta
authors.forename: Yurika
authors.initials: Y
authors.lastname: Agato
authors.forename: Dai
authors.initials: D
authors.lastname: Oyama
authors.forename: Nodoka
authors.initials: N
authors.lastname: Yasuda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Akira T
authors.initials: AT
authors.lastname: Kawaguchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D010316:Particle Size; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: D008081:Liposomes; D018696:Neuroprotective Agents