Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

Shantanu Balkundi¹, Ari S Nowacek¹, Ram S Veerubhotla¹, Han Chen², Andrea Martinez-Skinner¹, Upal Roy¹, R Lee Mosley^1,3, Georgette Kanmogne¹, Xinming Liu^1,3,4, Alexander V Kabanov^3,4, Tatiana Bronich^3,4, JoEllyn McMillan¹, Howard E Gendelman^1,3
1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; ²Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; ³Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; ⁴Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA

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.

Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques