Literature DB >> 31525692

A long acting nanoformulated lamivudine ProTide.

Nathan Smith1, Aditya N Bade1, Dhruvkumar Soni2, Nagsen Gautam2, Yazen Alnouti2, Jonathan Herskovitz1, Ibrahim M Ibrahim1, Melinda S Wojtkiewicz1, Bhagya Laxmi Dyavar Shetty1, JoEllyn McMillan1, Howard E Gendelman3, Benson Edagwa4.   

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.

Entities:  

Keywords:  Antiretroviral therapy; Formulation; Lamivudine; Long-acting; ProTide; Prodrug

Mesh：

Substances：

Year:  2019        PMID： 31525692      PMCID： PMC6945491          DOI： 10.1016/j.biomaterials.2019.119476

Source DB:  PubMed          Journal:  Biomaterials        ISSN： 0142-9612            Impact factor:   12.479


  53 in total

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