A long acting nanoformulated lamivudine ProTide

Nathan Smith, Aditya N. Bade, Dhruvkumar Soni, Nagsen Gautam, Yazen Alnouti, Jonathan Herskovitz, Ibrahim M. Ibrahim, Melinda S. Wojtkiewicz, Bhagya Laxmi Dyavar Shetty, Jo Ellyn McMillan, Howard E. Gendelman, Benson Edagwa

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Article number119476
StatePublished - Dec 2019


  • Antiretroviral therapy
  • Formulation
  • Lamivudine
  • Long-acting
  • ProTide
  • Prodrug

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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