Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.
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.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Ari S
AS
Nowacek
JoEllyn
J
McMillan
Reagan
R
Miller
Alec
A
Anderson
Barrett
B
Rabinow
Howard E
HE
Gendelman
D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage; D002478:Cells, Cultured; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D058726:Nanoconjugates; D036103:Nanotechnology / Q000379:methods; D009842:Oligopeptides / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D058726:Nanoconjugates; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; C098320:efavirenz; D019438:Ritonavir