title: Development and characterization of a long-acting nanoformulated abacavir prodrug.
abstract: A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability.
  
  
  
  Myristoylated ABC (MABC) was made by esterifying myristic acid to the drug's 5-hydroxy-cyclopentene group. Chemical composition, antiretroviral activity, cell uptake and retention and cellular trafficking of free MABC and poloxamer nanoformulations of MABC were assessed by proton nuclear magnetic resonance and tested in human monocyte-derived macrophages. Pharmacokinetics of ABC and nanoformulated MABC were evaluated after intramuscular injection into mice.
  
  
  
  MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks.
  
  
  
  MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Dhirender
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hilaire
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Nagsen
authors.initials: N
authors.lastname: Gautam
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Palandri
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yazen
authors.initials: Y
authors.lastname: Alnouti
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Benson
authors.initials: B
authors.lastname: Edagwa
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D003692:Delayed-Action Preparations; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D065546:Drug Liberation; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007273:Injections, Intramuscular; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000737:chemistry / Q000494:pharmacology; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D015224:Dideoxynucleosides; D020442:Poloxamer; D011355:Prodrugs; D019438:Ritonavir; D000099227:Abacavir
keywords: abacavir prodrug; antiretroviral therapy; monocyte-macrophages; nanoformulated antiretrovirals; pharmacokinetics