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 Y Poluektova, JoEllyn M McMillan, Howard Eliot Gendelman

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

Fingerprint

Folic Acid
HIV-1
Ritonavir
Intramuscular Injections
Viral RNA
CD4 Lymphocyte Count
Pharmaceutical Preparations
Nanoparticles
HIV Infections
Limit of Detection
HIV
T-Lymphocytes
Therapeutics

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

Cite this

Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice. / Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R Lee; Gorantla, Santhi; Poluektova, Larisa Y; McMillan, JoEllyn M; Gendelman, Howard Eliot.

In: Antiviral Research, Vol. 120, No. 1, 01.01.2015, p. 85-88.

Research output: Contribution to journalArticle

@article{cd0564a74b8e4ee291a8688e4d349203,
title = "Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice",
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.",
keywords = "Folic acid receptor, Human immunodeficiency virus type one, Long-acting nanoformulated antiretroviral therapy, Non-obese diabetic severe combined immunodeficient mice, Pharmacodynamics, Pharmacokinetics",
author = "Pavan Puligujja and Mariluz Ara{\'i}nga and Prasanta Dash and Diana Palandri and Mosley, {R Lee} and Santhi Gorantla and Poluektova, {Larisa Y} and McMillan, {JoEllyn M} and Gendelman, {Howard Eliot}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.antiviral.2015.05.009",
language = "English (US)",
volume = "120",
pages = "85--88",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice

AU - Puligujja, Pavan

AU - Araínga, Mariluz

AU - Dash, Prasanta

AU - Palandri, Diana

AU - Mosley, R Lee

AU - Gorantla, Santhi

AU - Poluektova, Larisa Y

AU - McMillan, JoEllyn M

AU - Gendelman, Howard Eliot

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Folic acid receptor

KW - Human immunodeficiency virus type one

KW - Long-acting nanoformulated antiretroviral therapy

KW - Non-obese diabetic severe combined immunodeficient mice

KW - Pharmacodynamics

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=84934967815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934967815&partnerID=8YFLogxK

U2 - 10.1016/j.antiviral.2015.05.009

DO - 10.1016/j.antiviral.2015.05.009

M3 - Article

VL - 120

SP - 85

EP - 88

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

IS - 1

ER -