Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

Shantanu Balkundi1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Ari S Nowacek1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Ram S Veerubhotla1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Han Chen2 Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA

Andrea Martinez-Skinner1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Upal Roy1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

R Lee Mosley1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA;3 Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA

Georgette Kanmogne1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Xinming Liu1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA;3 Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA;4 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA

Alexander V Kabanov3 Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA;4 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA

Tatiana Bronich3 Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA;4 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA

JoEllyn McMillan1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Howard E Gendelman1 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA;3 Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USACorrespondence[email protected]

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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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Acknowledgments

The work was supported by the National Institutes of Health grants 1P01 DA028555, 2R01 NS034239, 2R37 NS36126, P01 NS31492, P20RR 15635, P01MH64570, 5P20 RR021937 (AVK), and P01 NS43985 (HEG) and from a research grant from Baxter Healthcare. The authors thank Alec Anderson, Landon Ehlers, Yudong Li, and Nathan Smith for their expert technical assistance. The authors would also like to thank Dr You Zhou of the University of Nebraska-Lincoln electron microscopy core facility for supplying the scanning electron microscopy images.

Disclosure

The authors report no conflicts of interest in this work.

Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

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Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

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