title: Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain targeting liposomes.
abstract: The new bifunctional cluster glucosides were designed and synthesized as liposome ligands for preparing novel liposome to achieve the effective delivery of drug formulations to brain by GLUT1. Docetaxel-loaded five liposomes were prepared successfully and tested in the animals. Results from the in vivo distribution study after i.v. administration of these five liposomes and blank-docetaxel indicated that the coupled liposomes Lip-1, Lip-2, Lip-3, Lip-5 exhibited excellent transport ability across the BBB. In particular, they significantly increased the level of docetaxel in brain compared to blank-docetaxel and Lip. Among them, Lip-5 showed higher brain concentration. Both pharmacokinetics and distribution study in mice confirmed that this novel brain targeting drug delivery system was a promising carrier to enhance brain delivery capacity for CNS drugs.
authors.affiliation: Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Boyi
authors.initials: B
authors.lastname: Qu
authors.affiliation: Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xiaocen
authors.initials: X
authors.lastname: Li
authors.affiliation: West China Hospital, Sichuan University, No. 37, GuoXue Road, Chengdu 610041, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Guan
authors.affiliation: Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hai
authors.affiliation: Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: wyong@scu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000077143:Docetaxel; D015195:Drug Design; D005960:Glucosides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D043823:Taxoids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D005960:Glucosides; D008024:Ligands; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel
keywords: Brain targeting; Cholesterylated glucosides; GLUT1 transporter; Liposome; Synthesis