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

Huanyu Dou, Justin Morehead, Christopher J. Destache, Jeffrey D. Kingsley, Lyudmila Shlyakhtenko, You Zhou, Mahesh Chaubal, Jane Werling, James Kipp, Barrett E. Rabinow, Howard E. Gendelman

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79 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)148-158
Number of pages11
JournalVirology
Volume358
Issue number1
DOIs
StatePublished - Feb 5 2007

All Science Journal Classification (ASJC) codes

  • Virology

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    Dou, H., Morehead, J., Destache, C. J., Kingsley, J. D., Shlyakhtenko, L., Zhou, Y., Chaubal, M., Werling, J., Kipp, J., Rabinow, B. E., & Gendelman, H. E. (2007). Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages. Virology, 358(1), 148-158. https://doi.org/10.1016/j.virol.2006.08.012