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

J Neuroimmune Pharmacol. 2010 Dec;5(4):592-601. doi: 10.1007/s11481-010-9198-7. Epub 2010 Mar 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Anti-HIV Agents / administration & dosage*
  • Atazanavir Sulfate
  • Benzoxazines / administration & dosage
  • Cells, Cultured
  • Cyclopropanes
  • Delayed-Action Preparations
  • Drug Therapy, Combination
  • HIV Infections / drug therapy
  • HIV-1 / drug effects*
  • Humans
  • Immunohistochemistry
  • Macrophages / drug effects*
  • Macrophages / virology*
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoconjugates*
  • Nanotechnology / methods
  • Oligopeptides / administration & dosage
  • Pyridines / administration & dosage
  • Ritonavir / administration & dosage

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Delayed-Action Preparations
  • Nanoconjugates
  • Oligopeptides
  • Pyridines
  • Atazanavir Sulfate
  • efavirenz
  • Ritonavir