A long acting nanoformulated lamivudine ProTide

Biomaterials. 2019 Dec:223:119476. doi: 10.1016/j.biomaterials.2019.119476. Epub 2019 Sep 5.

Abstract

A long acting (LA) hydrophobic and lipophilic lamivudine (3TC) was created as a phosphoramidate pronucleotide (designated M23TC). M23TC improved intracellular delivery of active triphosphate metabolites and enhanced antiretroviral and pharmacokinetic (PK) profiles over the native drug. A single treatment of human monocyte derived macrophages (MDM) with nanoformulated M23TC (NM23TC) improved drug uptake, retention, intracellular 3TC triphosphates and antiretroviral activities in MDM and CD4+ T cells. PK tests of NM23TC administered to Sprague Dawley rats demonstrated sustained prodrug and drug triphosphate levels in blood and tissues for 30 days. The development of NM23TC remains a substantive step forward in producing LA slow effective release antiretrovirals for future clinical translation.

Keywords: Antiretroviral therapy; Formulation; Lamivudine; Long-acting; ProTide; Prodrug.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / administration & dosage*
  • CD4-Positive T-Lymphocytes / drug effects
  • Cells, Cultured
  • HIV Infections / drug therapy*
  • HIV-1
  • Humans
  • Lamivudine / administration & dosage*
  • Lymph Nodes / drug effects
  • Macrophages / drug effects*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Monocytes / drug effects*
  • Nanomedicine / methods
  • Nanoparticles / chemistry
  • Prodrugs
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Spleen / drug effects

Substances

  • Anti-HIV Agents
  • Prodrugs
  • Lamivudine