Nanoformulated Antiretroviral Drug Combinations Extend Drug Release and Antiretroviral Responses in HIV-1-Infected Macrophages: Implications for NeuroAIDS Therapeutics |
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Authors: | Ari S Nowacek JoEllyn McMillan Reagan Miller Alec Anderson Barrett Rabinow Howard E Gendelman |
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Institution: | (1) Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA;(2) Baxter Healthcare Corporation, Round Lake, IL 60073, USA; |
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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. |
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