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 journalArticle

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.

Original languageEnglish (US)
Article number119476
JournalBiomaterials
Volume223
DOIs
StatePublished - Dec 2019

Fingerprint

Pharmacokinetics
Lamivudine
Macrophages
T-cells
Metabolites
Pharmaceutical Preparations
Rats
Blood
Prodrugs
Tissue
Sprague Dawley Rats
T-Lymphocytes
triphosphoric acid

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Biomaterials, Vol. 223, 119476, 12.2019.

Research output: Contribution to journalArticle

Smith, N, Bade, AN, Soni, D, Gautam, N, Alnouti, Y, Herskovitz, J, Ibrahim, IM, Wojtkiewicz, MS, Dyavar Shetty, BL, McMillan, JE, Gendelman, HE & Edagwa, B 2019, 'A long acting nanoformulated lamivudine ProTide', Biomaterials, vol. 223, 119476. https://doi.org/10.1016/j.biomaterials.2019.119476
Smith N, Bade AN, Soni D, Gautam N, Alnouti Y, Herskovitz J et al. A long acting nanoformulated lamivudine ProTide. Biomaterials. 2019 Dec;223. 119476. https://doi.org/10.1016/j.biomaterials.2019.119476
Smith, Nathan ; Bade, Aditya N. ; Soni, Dhruvkumar ; Gautam, Nagsen ; Alnouti, Yazen ; Herskovitz, Jonathan ; Ibrahim, Ibrahim M. ; Wojtkiewicz, Melinda S. ; Dyavar Shetty, Bhagya Laxmi ; McMillan, Jo Ellyn ; Gendelman, Howard E. ; Edagwa, Benson. / A long acting nanoformulated lamivudine ProTide. In: Biomaterials. 2019 ; Vol. 223.
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