title: Comparative manufacture and cell-based delivery of antiretroviral nanoformulations.
abstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Balkundi
authors.forename: Ari S
authors.initials: AS
authors.lastname: Nowacek
authors.forename: Ram S
authors.initials: RS
authors.lastname: Veerubhotla
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinez-Skinner
authors.forename: Upal
authors.initials: U
authors.lastname: Roy
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Georgette
authors.initials: G
authors.lastname: Kanmogne
authors.forename: Xinming
authors.initials: X
authors.lastname: Liu
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bronich
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003521:Cyclopropanes; D006651:Histocytochemistry; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013010:Sonication
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019469:Indinavir; C098320:efavirenz; D019438:Ritonavir