A long-acting 3TC ProTide nanoformulation suppresses HBV replication in humanized mice

Weimin Wang, Nathan Smith, Edward Makarov, Yimin Sun, Catherine L. Gebhart, Murali Ganesan, Natalia A. Osna, Howard E. Gendelman, Benson J. Edagwa, Larisa Y. Poluektova

Research output: Contribution to journalArticle

Abstract

Nowadays, there is a strong request for the treatment of chronic HBV-infection with direct acting antivirals. Furthermore, prevalent human immunodeficiency virus (HIV-1) and hepatitis B (HBV) co-infections highlight an immediate need for dual long-acting and easily administered antivirals. To this end, we modified lamivudine (3TC), a nucleoside analog inhibitor of both viruses, into a lipophilic monophosphorylated prodrug (M23TC). Prior work demonstrated that nanoformulation of M23TC (NM23TC) enhanced drug stability, controlled dissolution and improved access to sites of viral replication. The present study evaluated the efficacy of a NM23TC in HBV-infected chimeric liver humanized mice. Levels of HBV DNA and HBsAg in plasma were monitored up to 8 weeks posttreatment. A single intramuscular dose of 75 mg/kg 3TC equivalents of nanoformulated NM23TC provided sustained drug levels and suppressed HBV replication in humanized mice for 4 weeks. The results support further development of this long-acting 3TC nanoformulation for HBV treatment and prevention.

Original languageEnglish (US)
Article number102185
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume28
DOIs
StatePublished - Aug 2020

Keywords

  • Hepatitis B virus (HBV)
  • Humanized liver mice
  • Lamivudine (3TC)
  • Long-acting nanoformulation
  • TK-NOG mice

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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