Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation

Ibrahim M. Ibrahim, Aditya N. Bade, Zhiyi Lin, Dhruvkumar Soni, Melinda Wojtkiewicz, Bhagya Laxmi Dyavar Shetty, Nagsen Gautam, Joellyn M. McMillan, Yazen Alnouti, Benson J. Edagwa, Howard E. Gendelman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Purpose: A palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug’s half-life, antiretroviral activities and biodistribution. Methods: A modified FTC prodrug (MFTC) was synthesized by palmitoyl chloride esterification. MFTC’s chemical structure was evaluated by nuclear magnetic resonance. The created hydrophobic prodrug nanocrystals were encased into a poloxamer surfactant and the pharmacokinetics (PK), biodistribution and antiretroviral activities of the nanoformulation (NMFTC) were assessed. The conversion of MFTC to FTC triphosphates was evaluated. Results: MFTC coated with poloxamer formed stable nanocrystals (NMFTC). NMFTC demonstrated an average particle size, polydispersity index and zeta potential of 350 nm, 0.24 and −20 mV, respectively. Drug encapsulation efficiency was 90%. NMFTC was readily taken up by human monocyte-derived macrophages yielding readily detected intracellular FTC triphosphates and an extended PK profile. Conclusion: NMFTC shows improved antiretroviral activities over native FTC. This is coordinate with its extended apparent half-life. The work represents an incremental advance in the development of a long-acting FTC formulation.

Original languageEnglish (US)
Pages (from-to)6231-6247
Number of pages17
JournalInternational journal of nanomedicine
StatePublished - 2019


  • Human immunodeficiency virus type 1
  • Long-acting antiretrovirals
  • Monocyte-derived macrophage
  • Palmitoyl chloride
  • Viral reservoirs

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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