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

Research output: Contribution to journalArticle

77 Citations (Scopus)

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

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Indinavir
Virus Diseases
Nanoparticles
Pharmacokinetics
Macrophages
HIV-1
HIV
Satellite Viruses
RNA-Directed DNA Polymerase
Giant Cells
Phagocytes
Vacuoles
Pharmaceutical Preparations
Therapeutics
Cell Culture Techniques
Antigens

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

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

In: Virology, Vol. 358, No. 1, 05.02.2007, p. 148-158.

Research output: Contribution to journalArticle

Dou, H, Morehead, J, Destache, CJ, Kingsley, JD, Shlyakhtenko, L, Zhou, Y, Chaubal, M, Werling, J, Kipp, J, Rabinow, BE & Gendelman, HE 2007, 'Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages', Virology, vol. 358, no. 1, pp. 148-158. https://doi.org/10.1016/j.virol.2006.08.012
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. / Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages. In: Virology. 2007 ; Vol. 358, No. 1. pp. 148-158.
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