1. A long acting nanoformulated lamivudine ProTide.
- Author
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Smith N, Bade AN, Soni D, Gautam N, Alnouti Y, Herskovitz J, Ibrahim IM, Wojtkiewicz MS, Dyavar Shetty BL, McMillan J, Gendelman HE, and Edagwa B
- Subjects
- Animals, CD4-Positive T-Lymphocytes drug effects, Cells, Cultured, HIV-1, Humans, Lymph Nodes drug effects, Magnetic Resonance Spectroscopy, Mice, Nanomedicine methods, Nanoparticles chemistry, Prodrugs, Rabbits, Rats, Rats, Sprague-Dawley, Spleen drug effects, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, Lamivudine administration & dosage, Macrophages drug effects, Monocytes drug effects
- 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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