Nanoformulated Antiretroviral Combinations Extend Drug Release and Antiretroviral Responses in HIV-1 Infected Macrophages: Implications for NeuroAIDS Therapeutics

摘要

We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus-type one infected people can be achieved through developments in nanoformulations. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies. 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 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.