Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: Implications for NeuroAIDS therapeutics

Ari S. Nowacek, Joellyn McMillan, Reagan Miller, Alec Anderson, Barrett Rabinow, Howard E. Gendelman

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.

Original languageEnglish (US)
Pages (from-to)592-601
Number of pages10
JournalJournal of Neuroimmune Pharmacology
Volume5
Issue number4
DOIs
StatePublished - Dec 1 2010

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Keywords

  • HIV
  • antiretroviral therapy
  • drug delivery
  • macrophages
  • nanomedicine
  • nanoparticles

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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