Vector-mediated drug delivery to the brain

被引:99
作者
Pardridge, WM [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
关键词
blood-brain barrier; insulin receptor; Alzheimer's disease; drug delivery; pharmacokinetics; avidin; biotin;
D O I
10.1016/S0169-409X(98)00087-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Vector-mediated drug delivery to the brain employs the chimeric peptide technology, wherein a non-transportable drug is conjugated to a blood-brain barrier (BBB) transport vector. The latter is a modified protein or receptor-specific monoclonal antibody that undergoes receptor-mediated transcytosis through the BBB in vivo. Conjugation of drug to transport vector is facilitated with either chemical linkers, avidin-biotin technology, polyethylene glycol linkers, or liposomes. Multiple classes of therapeutics have been delivered to the brain with the chimeric peptide technology, including peptide-based pharmaceuticals, such as a vasoactive intestinal peptide analog or neurotrophins such as brain-derived neurotrophic factor, antisense therapeutics including peptide nucleic acids, and small molecules incorporated within Liposomes. The successful delivery of a drug through the BBB in vivo requires special molecular formulation of the drug. Therefore, it is important to merge central nervous system drug discovery and delivery as early as possible in the overall CNS drug development process. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:299 / 321
页数:23
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