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 et al. · Biomaterials · 2019

basic_science · Level V

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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<sup>+</sup> 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.

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