title: Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood.
abstract: Insufficient HIV drug levels in lymph nodes have been linked to viral persistence. To overcome lymphatic drug insufficiency, we developed and evaluated in primates a lipid-drug nanoparticle containing lopinavir, ritonavir, and tenofovir. These nanoparticles produced over 50-fold higher intracellular lopinavir, ritonavir and tenofovir concentrations in lymph nodes compared to free drug. Plasma and intracellular drug levels in blood were enhanced and sustained for 7 days after a single subcutaneous dose, exceeding that achievable with current oral therapy.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Freeling
authors.forename: Josefin
authors.initials: J
authors.lastname: Koehn
authors.forename: Cuiling
authors.initials: C
authors.lastname: Shu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: Rodney J Y
authors.initials: RJ
authors.lastname: Ho
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001773:Blood Cells / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage; D004338:Drug Combinations; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000737:chemistry*; D008254:Macaca nemestrina; D053758:Nanoparticles / Q000008:administration & dosage*; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D004338:Drug Combinations; D063065:Organophosphonates; D061466:Lopinavir; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir
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