Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections

Pavan Puligujja, Jo Ellyn McMillan, Lindsey Kendrick, Tianyuzi Li, Shantanu Balkundi, Nathan Smith, Ram S. Veerubhotla, Benson J. Edagwa, Alexander V. Kabanov, Tatiana Bronich, Howard E. Gendelman, Xin Ming Liu

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, up to a five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. From the Clinical Editor: This team of authors describes a novel method for macrophage folate receptor-targeted antiretroviral therapy. Atazanvir entry, retention, and antiretroviral activities were superior using the presented method, and so was its biodistribution, enabling a more efficient way to address human immunodeficiency virus infections, with a hoped for clinical application in the near future.

Original languageEnglish (US)
Pages (from-to)1263-1273
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume9
Issue number8
DOIs
StatePublished - Nov 2013

Keywords

  • ATV/r
  • Folate
  • Human immunodeficiency virus
  • Macrophages
  • NanoART
  • Poloxamer 407
  • Targeted drug delivery

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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