PHARMACOLOGICAL EFFECTS INVIVO IN BRAIN BY VECTOR-MEDIATED PEPTIDE DRUG DELIVERY

被引：147

作者：

BICKEL, U

YOSHIKAWA, T

LANDAW, EM

FAULL, KF

PARDRIDGE, WM

机构：

[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024

[2] UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90024

[3] UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024

[4] UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90024

[5] UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1993年 / 90卷 / 07期

关键词：

VASOACTIVE INTESTINAL PEPTIDE; BLOOD-BRAIN BARRIER; CEREBRAL BLOOD FLOW;

D O I：

10.1073/pnas.90.7.2618

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 mug/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

引用

页码：2618 / 2622

页数：5

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