Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood

AIDS. 2014 Nov 13;28(17):2625-7. doi: 10.1097/QAD.0000000000000421.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adenine / pharmacokinetics
  • Animals
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics*
  • Blood Cells / chemistry*
  • Drug Carriers / administration & dosage
  • Drug Combinations
  • Lopinavir / administration & dosage
  • Lopinavir / pharmacokinetics
  • Lymph Nodes / chemistry*
  • Macaca nemestrina
  • Nanoparticles / administration & dosage*
  • Organophosphonates / administration & dosage
  • Organophosphonates / pharmacokinetics
  • Plasma / chemistry*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics
  • Tenofovir

Substances

  • Anti-HIV Agents
  • Drug Carriers
  • Drug Combinations
  • Organophosphonates
  • Lopinavir
  • Tenofovir
  • Adenine
  • Ritonavir