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A long acting nanoformulated lamivudine ProTide.

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.

SUBMITTER: Smith N

PROVIDER: S-EPMC6945491 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A long acting nanoformulated lamivudine ProTide.

Smith Nathan N Bade Aditya N AN Soni Dhruvkumar D Gautam Nagsen N Alnouti Yazen Y Herskovitz Jonathan J Ibrahim Ibrahim M IM Wojtkiewicz Melinda S MS Dyavar Shetty Bhagya Laxmi BL McMillan JoEllyn J Gendelman Howard E HE Edagwa Benson B

Biomaterials 20190905

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>+ ...[more]

PMID: 31525692

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