Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice

Pavan Puligujja, Mariluz Araínga, Prasanta Dash, Diana Palandri, R. Lee Mosley, Santhi Gorantla, Larisa Poluektova, Jo Ellyn McMillan, Howard E. Gendelman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Long-acting nanoformulated antiretroviral therapy (nanaoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100 mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use.

Original languageEnglish (US)
Pages (from-to)85-88
Number of pages4
JournalAntiviral Research
Volume120
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Folic acid receptor
  • Human immunodeficiency virus type one
  • Long-acting nanoformulated antiretroviral therapy
  • Non-obese diabetic severe combined immunodeficient mice
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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