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A long acting nanoformulated lamivudine ProTide. 2019
Nathan Smith, and
Aditya N Bade, and
Dhruvkumar Soni, and
Nagsen Gautam, and
Yazen Alnouti, and
Jonathan Herskovitz, and
Ibrahim M Ibrahim, and
Melinda S Wojtkiewicz, and
Bhagya Laxmi Dyavar Shetty, and
JoEllyn McMillan, and
Howard E Gendelman, and
Benson Edagwa
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
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.
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