Transformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles

Denise A. Cobb; Nathan Smith; Suyash Deodhar; Aditya N. Bade; Nagsen Gautam; Bhagya Laxmi Dyavar Shetty; JoEllyn McMillan; Yazen Alnouti; Samuel M. Cohen; Howard E. Gendelman; Benson Edagwa

doi:10.1038/s41467-021-25690-5

Nature Communications (Sep 2021)

Transformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles

Denise A. Cobb,
Nathan Smith,
Suyash Deodhar,
Aditya N. Bade,
Nagsen Gautam,
Bhagya Laxmi Dyavar Shetty,
JoEllyn McMillan,
Yazen Alnouti,
Samuel M. Cohen,
Howard E. Gendelman,
Benson Edagwa

Affiliations

Denise A. Cobb: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Nathan Smith: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Suyash Deodhar: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Aditya N. Bade: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Nagsen Gautam: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Bhagya Laxmi Dyavar Shetty: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
JoEllyn McMillan: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Yazen Alnouti: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Samuel M. Cohen: Department of Pathology and Microbiology, University of Nebraska Medical Center
Howard E. Gendelman: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Benson Edagwa: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center

DOI: https://doi.org/10.1038/s41467-021-25690-5
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 16

Abstract

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Antiretroviral therapy (ART) for the treatment of HIV-1 requires life-long daily adherence to supress viral replication, and nucleoside reverse transcriptase inhibitors that are commonly used in ART have not been converted into long-acting agents. Here, the authors report two lipophilic tenofovir (TVF) ProTide nanoformulations, NM1TFV and NM2TFV, which sustain drug levels above therapeutic concentrations for two months after a single intramuscular dose in rats.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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