Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

抗逆转录病毒纳米制剂的比较制造和基于细胞的递送

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作者:Shantanu Balkundi, Ari S Nowacek, Ram S Veerubhotla, Han Chen, Andrea Martinez-Skinner, Upal Roy, R Lee Mosley, Georgette Kanmogne, Xinming Liu, Alexander V Kabanov, Tatiana Bronich, JoEllyn McMillan, Howard E Gendelman

Abstract

Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.

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