In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes.
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.
Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.
Yao
Y
Qin
Wei
W
Fan
Huali
H
Chen
Nian
N
Yao
Wenwei
W
Tang
Jie
J
Tang
Wenmin
W
Yuan
Rui
R
Kuai
Zhirong
Z
Zhang
Yong
Y
Wu
Qin
Q
He
D000818:Animals; D019540:Area Under Curve; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry*; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003374:Coumarins; D051246:Glucose Transport Proteins, Facilitative; D008081:Liposomes; D013844:Thiazoles; C517282:coumarin 6; D002784:Cholesterol