Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human nomocyte-derived macrophages

被引：68

作者：

Dou, Huanyu

Morehead, Justin

Destache, Christopher J.

Kingsley, Jeffrey D.

Shlyakhtenko, Lyudmila

Zhou, You

Chaubal, Mahesh

Werling, Jane

Kipp, James

Rabinow, Barrett E.

Gendelman, Howard E.

机构：

[1] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA

[2] Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA

[3] Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA

[4] Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE 68198 USA

[5] Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA

[6] Univ Nebraska, Dept Vet & Biomed Sci, Lincoln, NE 68588 USA

[7] Creighton Univ, Sch Pharm & Hlth Profess, Omaha, NE 68178 USA

[8] Baxter Healthcare Corp, Round Lake, IL 60073 USA

来源：

VIROLOGY | 2007年 / 358卷 / 01期

关键词：

macrophages; nanoparticles; anti-retroviral efficacy; human immunodeficiency virus; indinavir;

D O I：

10.1016/j.virol.2006.08.012

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle-indinavir (NP-IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP-IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP-IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide "proof of concept" for the use of macrophage-based NP delivery systems for human HIV-1 infections. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：148 / 158

页数：11

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[51] Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment [J].