Long-acting nanoformulated antiretroviral therapy (nanoART) 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, 100mg/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.
Animals, Anti-Retroviral Agents, Atazanavir Sulfate, CD4 Lymphocyte Count, Delayed-Action Preparations, Drug Carriers, Folate Receptors, GPI-Anchored, Folic Acid, HIV Infections, Humans, Injections, Intramuscular, Mice, SCID, Nanomedicine, Nanoparticles, Poloxamer, RNA, Viral, Ritonavir, Treatment Outcome, Viral Load
This is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including peer review, editing and formatting, might not be reflected in this document. A definitive version was published in Antiviral Therapy, (120, p. 85-88), August, ©2015 International Medical Press."
Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana L.; Mosley, R. Lee; Gorantla, Santhi; Poluektova, Larisa Y; McMillan, JoEllyn; and Gendelman, Howard, "Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice." (2015). Journal Articles: Pharmacology & Experimental Neuroscience. 24.