TY - JOUR
T1 - Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages
AU - Dou, Huanyu
AU - Morehead, Justin
AU - Destache, Christopher J.
AU - Kingsley, Jeffrey D.
AU - Shlyakhtenko, Lyudmila
AU - Zhou, You
AU - Chaubal, Mahesh
AU - Werling, Jane
AU - Kipp, James
AU - Rabinow, Barrett E.
AU - Gendelman, Howard E.
N1 - Funding Information:
The project described was supported by NIH Grants: 1 T32 NS07488-01, 5 R37 NS36126-07, 5 R01 NS034239-10, 1 P01 NS43985-01A1, 5 P01NS31492-11, 5 P01 MH64570-03, P01 NS11766-28 and 20 RR15635 from the National Center for Research Resources. The authors extend a special thanks to Ms. Robin Taylor for outstanding administrative and editorial support and Dr. Tatiana K. Bronich for helpful discussions and specific suggestions that made possible the rDHPE-NP-IDV cell labelings.
PY - 2007/2/5
Y1 - 2007/2/5
N2 - The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle-indinavir (NP-IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP-IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP-IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide "proof of concept" for the use of macrophage-based NP delivery systems for human HIV-1 infections.
AB - The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle-indinavir (NP-IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP-IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP-IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide "proof of concept" for the use of macrophage-based NP delivery systems for human HIV-1 infections.
KW - Anti-retroviral efficacy
KW - Human immunodeficiency virus
KW - Indinavir
KW - Macrophages
KW - Nanoparticles
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U2 - 10.1016/j.virol.2006.08.012
DO - 10.1016/j.virol.2006.08.012
M3 - Article
C2 - 16997345
AN - SCOPUS:33845965983
SN - 0042-6822
VL - 358
SP - 148
EP - 158
JO - Virology
JF - Virology
IS - 1
ER -