Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir

Nagsen Gautam; JoEllyn M. McMillan; Devendra Kumar; Aditya N. Bade; Qiaoyu Pan; Tanmay A. Kulkarni; Wenkuan Li; Brady Sillman; Nathan A. Smith; Bhagya L. Dyavar Shetty; Adam Szlachetka; Benson J. Edagwa; Howard E. Gendelman; Yazen Alnouti

doi:10.1038/s41467-021-23668-x

Nature Communications (Jun 2021)

Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir

Nagsen Gautam,
JoEllyn M. McMillan,
Devendra Kumar,
Aditya N. Bade,
Qiaoyu Pan,
Tanmay A. Kulkarni,
Wenkuan Li,
Brady Sillman,
Nathan A. Smith,
Bhagya L. Dyavar Shetty,
Adam Szlachetka,
Benson J. Edagwa,
Howard E. Gendelman,
Yazen Alnouti

Affiliations

Nagsen Gautam: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
JoEllyn M. McMillan: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Devendra Kumar: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Aditya N. Bade: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Qiaoyu Pan: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Tanmay A. Kulkarni: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Wenkuan Li: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Brady Sillman: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Nathan A. Smith: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Bhagya L. Dyavar Shetty: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Adam Szlachetka: Nebraska Nanomedicine Production Plant, University of Nebraska Medical Center
Benson J. Edagwa: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Howard E. Gendelman: Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Yazen Alnouti: Department of Pharmaceutical Sciences, University of Nebraska Medical Center

DOI: https://doi.org/10.1038/s41467-021-23668-x
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 13

Abstract

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Here, the authors provide a mechanism for an improved version of a nanoformulated myristoylated prodrug of cabotegravir (CAB), named NM2CAB, and its bioavailability, stability and pharmacokinetics in mice and rats performed in independent academic and a contracted research labs, suggesting that the extended half-life of the prodrug is not a property of enzymatic hydrolysis but rather release or dissolution of the prodrug from the nanocrystal.

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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