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Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain
Boyi Qu1, Xiaocen Li1, Mei Guan2
1Key Laboratory of Drug Targeting of Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
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.
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