Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil

被引：62

作者：

Fukuta, Tatsuya ^{[1
,2
]}

Asai, Tomohiro ^{[1
]}

Sato, Akihiko ^{[1
]}

Namba, Mio ^{[1
]}

Yanagida, Yosuke ^{[1
]}

Kikuchi, Takashi ^{[1
]}

Koide, Hiroyuki ^{[1
]}

Shimizu, Kosuke ^{[1
]}

Oku, Naoto ^{[1
]}

机构：

[1] Univ Shizuoka, Sch Pharmaceut Sci, Dept Med Biochem, Suruga Ku, 52-1 Yada, Shizuoka 4228526, Japan

[2] Japan Soc Promot Sci, Chiyoda Ku, 5-3-1 Kojimachi, Tokyo 1020083, Japan

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2016年 / 506卷 / 1-2期

基金：

日本学术振兴会;

关键词：

Ischemic stroke; Cerebral ischemia/reperfusion injury; Liposomes; Fasudil; Blood-brain barrier; Middle cerebral artery occlusion; ISCHEMIA-REPERFUSION INJURY; BRAIN-BARRIER DISRUPTION; DRUG-DELIVERY SYSTEM; RHO-KINASE; ASIALO-ERYTHROPOIETIN; PEGYLATED LIPOSOMES; FOCAL STROKE; BLOOD-FLOW; INFLAMMATION; INHIBITION;

D O I：

10.1016/j.ijpharm.2016.04.046

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Fasudil, a Rho-kinase inhibitor, is a promising neuroprotectant against ischemic stroke; however, its low bioavailability is an obstacle to be overcome. Our previous study revealed that the liposomal drug delivery system is a hopeful strategy to increase the therapeutic efficacy of neuroprotectants. In the present study, the usefulness of intravenously administered liposomal fasudil for cerebral ischemia/reperfusion (I/R) injury treatment was examined in transient middle cerebral artery occlusion (t-MCAO) rats. The results showed that PEGylated liposomes of approximately 100 nm in diameter accumulated more extensively in the I/R region compared with those of over 200 nm. Confocal images showed that fluorescence-labeled liposomal fasudil was widely distributed in the I/R region, and was not noticeably taken up by microglia, which are well-known resident macrophages in the brain, and neuronal cells. These data indicated that liposomal fasudil mainly exerted its pharmacological activity by releasing fasudil from the liposomes in the I/R region. Moreover, liposomal fasudil effectively suppressed neutrophil invasion and brain cell damage in the t-MCAO rats, resulting in amelioration of their motor function deficits. These findings demonstrated both the importance of particle size for neuroprotectant delivery and the effectiveness of liposomal fasudil for the treatment of cerebral I/R injury. (c) 2016 Elsevier B.V. All rights reserved.

引用

页码：129 / 137

页数：9

共 35 条

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