Abstract
The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle–indinavir (NP–IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP–IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP–IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide “proof of concept” for the use of macrophage-based NP delivery systems for human HIV-1 infections.
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