TY - JOUR
T1 - Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages
AU - Nowacek, Ari S.
AU - Balkundi, Shantanu
AU - McMillan, Joellyn
AU - Roy, Upal
AU - Martinez-Skinner, Andrea
AU - Mosley, R. Lee
AU - Kanmogne, Georgette
AU - Kabanov, Alexander V.
AU - Bronich, Tatiana
AU - Gendelman, Howard E.
N1 - Funding Information:
The work was supported by the National Institutes of Health grants 1P01 DA028555 , 2R01 NS034239 , 2R37 NS36126 , P01 NS31492 , P20RR 15635 , P01MH64570 , and P01 NS43985 (to H.E.G.) and from a research grant from Baxter Healthcare . The authors thank Ms. Robin Taylor for critical reading of the manuscript and outstanding graphic and literary support. The authors also would like to thank Dr. Han Chen and Dr. You Zhou of the University of Nebraska-Lincoln electron microscopy core facility for supplying the scanning and transmission electron microscopy images. The authors would also like to thank Megan Marquardt and LeAnn Tiede for assistance in acquiring the live-cell confocal microscopy videos.
PY - 2011/3/10
Y1 - 2011/3/10
N2 - 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.
AB - 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.
KW - Antiretroviral
KW - Crystalline
KW - HIV
KW - Macrophage
KW - Monocyte
KW - Nanomedicine
KW - Nanoparticles
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U2 - 10.1016/j.jconrel.2010.11.019
DO - 10.1016/j.jconrel.2010.11.019
M3 - Article
C2 - 21108978
AN - SCOPUS:79952985878
SN - 0168-3659
VL - 150
SP - 204
EP - 211
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -