Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages

JOURNAL OF CONTROLLED RELEASE

卷:150

Article

Nowacek, Ari S.¹  Balkundi, Shantanu¹  McMillan, JoEllyn¹  Roy, Upal¹  Martinez-Skinner, Andrea¹  Mosley, R. Lee^1,3  Kanmogne, Georgette¹  Kabanov, Alexander V.^2,3  Bronich, Tatiana^2,3  Gendelman, Howard E.^1,3 

[1] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Coll Pharm, Omaha, NE 68198 USA

[3] Univ Nebraska Med Ctr, Ctr Drug Delivery & Nanomed, Omaha, NE 68198 USA

关键词: Antiretroviral;    Nanoparticles;    HIV;    Crystalline;    Macrophage;    Monocyte;    Nanomedicine;   

DOI  :  10.1016/j.jconrel.2010.11.019

来源: Elsevier

【 摘 要 】

Long-term antiretroviral therapy (ART) for human immunodeficiency virus type one (HIV-1) infection shows limitations in pharmacokinetics and biodistribution while inducing metabolic and cytotoxic aberrations. In turn, ART commonly requires complex dosing schedules and leads to the emergence of viral resistance and treatment failures. We posit that the development of nanoformulated ART could preclude such limitations and affect improved clinical outcomes. To this end, we wet-milled 20 nanoparticle formulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz, collectively referred to as nanoART, then assessed their performance using a range of physicochemical and biological tests. These tests were based on cell-nanoparticle interactions using monocyte-derived macrophages and their abilities to uptake and release nanoformulated drugs and affect viral replication. We demonstrate that physical characteristics such as particle size, surfactant coating, surface charge, and most importantly shape are predictors of cell uptake and antiretroviral efficacy. These studies bring this line of research a step closer to developing nanoART that can be used in the clinic to affect the course of HIV-1 infection. (C) 2010 Elsevier B.V. All rights reserved.

【 授权许可】

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