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

Ari S. Nowacek, Shantanu Balkundi, JoEllyn M McMillan, Upal Roy, Andrea Martinez-Skinner, R Lee Mosley, Georgette D Kanmogne, Alexander V. Kabanov, Tatiana K Bronich, Howard Eliot Gendelman

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalJournal of Controlled Release
Volume150
Issue number2
DOIs
StatePublished - Mar 10 2011

Fingerprint

Human Activities
Antiviral Agents
efavirenz
Macrophages
Nanoparticles
HIV Infections
HIV-1
Pharmaceutical Preparations
Indinavir
Ritonavir
Cell Shape
Treatment Failure
Particle Size
Surface-Active Agents
Cell Communication
Appointments and Schedules
Therapeutics
Pharmacokinetics
HIV
Research

Keywords

  • Antiretroviral
  • Crystalline
  • HIV
  • Macrophage
  • Monocyte
  • Nanomedicine
  • Nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "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.",
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AU - Nowacek, Ari S.

AU - Balkundi, Shantanu

AU - McMillan, JoEllyn M

AU - Roy, Upal

AU - Martinez-Skinner, Andrea

AU - Mosley, R Lee

AU - Kanmogne, Georgette D

AU - Kabanov, Alexander V.

AU - Bronich, Tatiana K

AU - Gendelman, Howard Eliot

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