Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages.
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.
Dou
Huanyu
H
Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Morehead
Justin
J
Destache
Christopher J
CJ
Kingsley
Jeffrey D
JD
Shlyakhtenko
Lyudmila
L
Zhou
You
Y
Chaubal
Mahesh
M
Werling
Jane
J
Kipp
James
J
Rabinow
Barrett E
BE
Gendelman
Howard E
HE
D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002459:Cell Fusion; D002470:Cell Survival; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections; D054303:HIV Reverse Transcriptase / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D019469:Indinavir; D054303:HIV Reverse Transcriptase