Methods development for blood borne macrophage carriage of nanoformulated antiretroviral drugs

Shantanu Balkundi, Ari S. Nowacek, Upal Roy, Andrea Martinez-Skinner, JoEllyn M McMillan, Howard Eliot Gendelman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes.

Original languageEnglish (US)
Article numbere2460
JournalJournal of Visualized Experiments
Issue number46
DOIs
StatePublished - Dec 2010

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Macrophages
Blood
Viruses
Toxicity
Pharmacodynamics
Pharmaceutical Preparations
Medical nanotechnology
Pharmacokinetics
Dynamic light scattering
Polymers
Cytotoxicity
Lipids
Compliance
Medicine
Purification
Microscopic examination
Surface active agents
Physical properties
Particle size
Nanomedicine

Keywords

  • Antiretroviral
  • HIV/AIDS
  • Homogenization
  • Immunology
  • Issue 46
  • Monocytes/macrophages
  • NanoART
  • Ultrasonication
  • Wet milling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Methods development for blood borne macrophage carriage of nanoformulated antiretroviral drugs. / Balkundi, Shantanu; Nowacek, Ari S.; Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn M; Gendelman, Howard Eliot.

In: Journal of Visualized Experiments, No. 46, e2460, 12.2010.

Research output: Contribution to journalArticle

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