title: Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Puligujja
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Mariluz
authors.initials: M
authors.lastname: Araínga
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Prasanta
authors.initials: P
authors.lastname: Dash
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Palandri
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Poluektova
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. Electronic address: hegendel@unmc.edu.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics; D018791:CD4 Lymphocyte Count; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007273:Injections, Intramuscular; D016513:Mice, SCID; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D020442:Poloxamer / Q000008:administration & dosage / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D012367:RNA, Viral; D020442:Poloxamer; D000069446:Atazanavir Sulfate; D005492:Folic Acid; D019438:Ritonavir
keywords: Folic acid receptor; Human immunodeficiency virus type one; Long-acting nanoformulated antiretroviral therapy; Non-obese diabetic severe combined immunodeficient mice; Pharmacodynamics; Pharmacokinetics