In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes

被引：92

作者：

Qin, Yao ^{[1
,2
]}

Fan, Wei ^{[1
]}

Chen, Huali ^{[1
]}

Yao, Nian ^{[1
]}

Tang, Wenwei ^{[1
]}

Tang, Jie ^{[1
]}

Yuan, Wenmin ^{[1
]}

Kuai, Rui ^{[1
]}

Zhang, Zhirong ^{[1
]}

Wu, Yong ^{[1
]}

He, Qin ^{[1
]}

机构：

[1] Sichuan Univ, W China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Chengdu 610041, Peoples R China

[2] TAIJI Grp, Chongqing, Peoples R China

来源：

JOURNAL OF DRUG TARGETING | 2010年 / 18卷 / 07期

关键词：

Biodistribution; blood-brain barrier; brain targeting; cytotoxicity; glucose; liposome; transendothelial; CENTRAL-NERVOUS-SYSTEM; ANTICONVULSANT ACTIVITY; 7-CHLOROKYNURENIC ACID; DRUG-DELIVERY; TRANSPORT; BARRIER; NANOPARTICLES; EXPRESSION; DERIVATIVES; AGENTS;

D O I：

10.3109/10611861003587235

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C-max of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.

引用

页码：536 / 549

页数：14

共 37 条

[1] Systemically administered D-glucose conjugates of 7-chlorokynurenic acid are centrally available and exert anticonvulsant activity in rodents [J].