Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation

Ibrahim M Ibrahim,1,2 Aditya N Bade,1 Zhiyi Lin,3 Dhruvkumar Soni,3 Melinda Wojtkiewicz,1 Bhagya Laxmi Dyavar Shetty,1 Nagsen Gautam,3 JoEllyn M McMillan,1 Yazen Alnouti,3 Benson J Edagwa,1 Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, College of Medicine, Universit...

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Autores principales:	Ibrahim IM, Bade AN, Lin Z, Soni D, Wojtkiewicz M, Dyavar Shetty BL, Gautam N, McMillan JM, Alnouti Y, Edagwa BJ, Gendelman HE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Palmitoyl chloride viral reservoirs long-acting antiretrovirals human immunodeficiency virus type 1 and monocyte-derived macrophage Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c4157bc83b334458acb808ffde41b91f
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spelling	oai:doaj.org-article:c4157bc83b334458acb808ffde41b91f2021-12-02T04:29:38ZSynthesis and characterization of a long-acting emtricitabine prodrug nanoformulation1178-2013https://doaj.org/article/c4157bc83b334458acb808ffde41b91f2019-08-01T00:00:00Zhttps://www.dovepress.com/synthesis-and-characterization-of-a-long-acting-emtricitabine-prodrug--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ibrahim M Ibrahim,1,2 Aditya N Bade,1 Zhiyi Lin,3 Dhruvkumar Soni,3 Melinda Wojtkiewicz,1 Bhagya Laxmi Dyavar Shetty,1 Nagsen Gautam,3 JoEllyn M McMillan,1 Yazen Alnouti,3 Benson J Edagwa,1 Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Pharmacology, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAPurpose: A palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug’s half-life, antiretroviral activities and biodistribution.Methods: A modified FTC prodrug (MFTC) was synthesized by palmitoyl chloride esterification. MFTC’s chemical structure was evaluated by nuclear magnetic resonance. The created hydrophobic prodrug nanocrystals were encased into a poloxamer surfactant and the pharmacokinetics (PK), biodistribution and antiretroviral activities of the nanoformulation (NMFTC) were assessed. The conversion of MFTC to FTC triphosphates was evaluated.Results: MFTC coated with poloxamer formed stable nanocrystals (NMFTC). NMFTC demonstrated an average particle size, polydispersity index and zeta potential of 350 nm, 0.24 and −20 mV, respectively. Drug encapsulation efficiency was 90%. NMFTC was readily taken up by human monocyte-derived macrophages yielding readily detected intracellular FTC triphosphates and an extended PK profile.Conclusion: NMFTC shows improved antiretroviral activities over native FTC. This is coordinate with its extended apparent half-life. The work represents an incremental advance in the development of a long-acting FTC formulation.Keywords: palmitoyl chloride, viral reservoirs, long-acting antiretrovirals, human immunodeficiency virus type 1, monocyte-derived macrophageIbrahim IMBade ANLin ZSoni DWojtkiewicz MDyavar Shetty BLGautam NMcMillan JMAlnouti YEdagwa BJGendelman HEDove Medical PressarticlePalmitoyl chlorideviral reservoirslong-acting antiretroviralshuman immunodeficiency virus type 1and monocyte-derived macrophageMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6231-6247 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Palmitoyl chloride viral reservoirs long-acting antiretrovirals human immunodeficiency virus type 1 and monocyte-derived macrophage Medicine (General) R5-920
spellingShingle	Palmitoyl chloride viral reservoirs long-acting antiretrovirals human immunodeficiency virus type 1 and monocyte-derived macrophage Medicine (General) R5-920 Ibrahim IM Bade AN Lin Z Soni D Wojtkiewicz M Dyavar Shetty BL Gautam N McMillan JM Alnouti Y Edagwa BJ Gendelman HE Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
description	Ibrahim M Ibrahim,1,2 Aditya N Bade,1 Zhiyi Lin,3 Dhruvkumar Soni,3 Melinda Wojtkiewicz,1 Bhagya Laxmi Dyavar Shetty,1 Nagsen Gautam,3 JoEllyn M McMillan,1 Yazen Alnouti,3 Benson J Edagwa,1 Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Pharmacology, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAPurpose: A palmitoylated prodrug of emtricitabine (FTC) was synthesized to extend the drug’s half-life, antiretroviral activities and biodistribution.Methods: A modified FTC prodrug (MFTC) was synthesized by palmitoyl chloride esterification. MFTC’s chemical structure was evaluated by nuclear magnetic resonance. The created hydrophobic prodrug nanocrystals were encased into a poloxamer surfactant and the pharmacokinetics (PK), biodistribution and antiretroviral activities of the nanoformulation (NMFTC) were assessed. The conversion of MFTC to FTC triphosphates was evaluated.Results: MFTC coated with poloxamer formed stable nanocrystals (NMFTC). NMFTC demonstrated an average particle size, polydispersity index and zeta potential of 350 nm, 0.24 and −20 mV, respectively. Drug encapsulation efficiency was 90%. NMFTC was readily taken up by human monocyte-derived macrophages yielding readily detected intracellular FTC triphosphates and an extended PK profile.Conclusion: NMFTC shows improved antiretroviral activities over native FTC. This is coordinate with its extended apparent half-life. The work represents an incremental advance in the development of a long-acting FTC formulation.Keywords: palmitoyl chloride, viral reservoirs, long-acting antiretrovirals, human immunodeficiency virus type 1, monocyte-derived macrophage
format	article
author	Ibrahim IM Bade AN Lin Z Soni D Wojtkiewicz M Dyavar Shetty BL Gautam N McMillan JM Alnouti Y Edagwa BJ Gendelman HE
author_facet	Ibrahim IM Bade AN Lin Z Soni D Wojtkiewicz M Dyavar Shetty BL Gautam N McMillan JM Alnouti Y Edagwa BJ Gendelman HE
author_sort	Ibrahim IM
title	Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
title_short	Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
title_full	Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
title_fullStr	Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
title_full_unstemmed	Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
title_sort	synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/c4157bc83b334458acb808ffde41b91f
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Synthesis and characterization of a long-acting emtricitabine prodrug nanoformulation

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