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A long acting nanoformulated lamivudine ProTide.
Biomaterials 2019; 223:119476B

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.

Authors+Show Affiliations

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: hegendel@unmc.edu.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: benson.edagwa@unmc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31525692

Citation

Smith, Nathan, et al. "A Long Acting Nanoformulated Lamivudine ProTide." Biomaterials, vol. 223, 2019, p. 119476.
Smith N, Bade AN, Soni D, et al. A long acting nanoformulated lamivudine ProTide. Biomaterials. 2019;223:119476.
Smith, N., Bade, A. N., Soni, D., Gautam, N., Alnouti, Y., Herskovitz, J., ... Edagwa, B. (2019). A long acting nanoformulated lamivudine ProTide. Biomaterials, 223, p. 119476. doi:10.1016/j.biomaterials.2019.119476.
Smith N, et al. A Long Acting Nanoformulated Lamivudine ProTide. Biomaterials. 2019;223:119476. PubMed PMID: 31525692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A long acting nanoformulated lamivudine ProTide. AU - Smith,Nathan, AU - Bade,Aditya N, AU - Soni,Dhruvkumar, AU - Gautam,Nagsen, AU - Alnouti,Yazen, AU - Herskovitz,Jonathan, AU - Ibrahim,Ibrahim M, AU - Wojtkiewicz,Melinda S, AU - Dyavar Shetty,Bhagya Laxmi, AU - McMillan,JoEllyn, AU - Gendelman,Howard E, AU - Edagwa,Benson, Y1 - 2019/09/05/ PY - 2019/03/27/received PY - 2019/08/06/revised PY - 2019/09/04/accepted PY - 2019/9/17/pubmed PY - 2019/9/17/medline PY - 2019/9/17/entrez KW - Antiretroviral therapy KW - Formulation KW - Lamivudine KW - Long-acting KW - ProTide KW - Prodrug SP - 119476 EP - 119476 JF - Biomaterials JO - Biomaterials VL - 223 N2 - 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. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/31525692/A_long_acting_nanoformulated_lamivudine_ProTide L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(19)30575-7 DB - PRIME DP - Unbound Medicine ER -