TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs

被引：245

作者：

Rao, Kavitha S. ^{[1
,2
]}

Reddy, Mararn K. ^{[1
]}

Horning, Jayrne L. ^{[2
]}

Labhasetwar, Vinod ^{[1
,2
]}

机构：

[1] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA

[2] Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA

来源：

BIOMATERIALS | 2008年 / 29卷 / 33期

基金：

美国国家卫生研究院;

关键词：

Trans-activating transcriptor; Nanoparticles; Blood-brain-barrier; P-glycoprotein; Transport; Anti-HIV drugs;

D O I：

10.1016/j.biomaterials.2008.08.004

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

We have shown that nanoparticles (NPs) conjugated to trans-activating transcriptor (TAT) peptide bypass the efflux action of P-glycoprotein and increase the transport of the encapsulated ritonavir, a protease inhibitor (PI), across the blood-brain-barrier (BBB) to the central nervous system (CNS). A steady increase in the drug parenchyma/capillary ratio over time without disrupting the BBB integrity suggests that TAT-conjugated NPs are first immobilized in the brain vasculature prior to their transport into parenchyma. Localization of NPs in the brain parenchyma was further confirmed with histological analysis of the brain sections. The brain drug level with conjugated NPs was 800-fold higher than that with drug in solution at two weeks. Drug clearance was seen within four weeks. in conclusion, TAT-conjugated NPs enhanced the CNS bioavailability of the encapsulated PI and maintained therapeutic drug levels in the brain for a sustained period that could be effective in reducing the viral load in the CNS, which acts as a reservoir for the replicating HIV-1 virus. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4429 / 4438

页数：10

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