Methods development for blood borne macrophage carriage of nanoformulated antiretroviral drugs

Shantanu Balkundi, Ari S. Nowacek, Upal Roy, Andrea Martinez-Skinner, Jo Ellyn McMillan, Howard E. Gendelman

Research output: Contribution to journalArticle

17 Scopus citations

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

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)

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