title: Biophysical characterization of small molecule antiviral-loaded nanolipogels for HIV-1 chemoprophylaxis and topical mucosal application.
abstract: Nanocarriers are versatile vehicles for drug delivery, and emerging as platforms to formulate and deliver multiple classes of antiretroviral (ARV) drugs in a single system. Here we describe the fabrication of hydrogel-core and lipid-shell nanoparticles (nanolipogels) for the controlled loading and topical, vaginal delivery of maraviroc (MVC) and tenofovir disoproxil fumarate (TDF), two ARV drugs with different mechanisms of action that are used in the treatment of HIV. The nanolipogel platform was used to successfully formulate MVC and TDF, which produced ARV drug-loaded nanolipogels that were characterized for their physical properties and antiviral activity against HIV-1 BaL in cell culture. We also show that administration of these drug carriers topically to the vaginal mucosa in a murine model leads to antiviral activity against HIV-1 BaL in cervicovaginal lavages. Our results suggest that nanolipogel carriers are promising for the encapsulation and delivery of hydrophilic small molecule ARV drugs, and may expand the nanocarrier systems being investigated for HIV prevention or treatment.
  
  
  
  Topical, mucosal intervention of HIV is a leading strategy in the efforts to curb the spread of viral infection. A significant research thrust in the field has been to characterize different dosage forms for formulation of physicochemically diverse antiretroviral drugs. Nanocarriers have been used to formulate and deliver small molecule and protein drugs for a range of applications, including ARV drugs for HIV treatment. The broad significance of our work includes evaluation of lipid-shell, hydrogel-core nanoparticles for formulation and topical, vaginal delivery of two water-soluble antiretroviral drugs. We have characterized these nanocarriers for their physical properties and their biological activity against HIV-1 infection in vitro, and demonstrated the ability to deliver drug-loaded nanocarriers in vivo.
authors.affiliation: 3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: renukar@uw.edu.
authors.forename: R
authors.initials: R
authors.lastname: Ramanathan
authors.affiliation: 3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: yhj@uw.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: readb2@uw.edu.
authors.forename: B
authors.initials: B
authors.lastname: Read
authors.affiliation: 3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: shagolan@uw.edu.
authors.forename: S
authors.initials: S
authors.lastname: Golan-Paz
authors.affiliation: 3720 15th Ave NE, Foege Hall, Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: woodrow@uw.edu.
authors.forename: K A
authors.initials: KA
authors.lastname: Woodrow
mesh_terms: D000287:Administration, Topical; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D055592:Biophysical Phenomena; D001826:Body Fluids / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D020285:Cryoelectron Microscopy; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology; D003902:Detergents / Q000737:chemistry; D065546:Drug Liberation; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes; D000077592:Maraviroc; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D054852:Small Molecule Libraries / Q000494:pharmacology*; D000068698:Tenofovir / Q000008:administration & dosage / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D003902:Detergents; D008051:Lipid Bilayers; D008081:Liposomes; D054852:Small Molecule Libraries; D014230:Triazoles; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000068698:Tenofovir; D000077592:Maraviroc
keywords: Chemoprophylaxis; Liposomes; Maraviroc; Nanoparticles; TDF