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A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis.

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Date
2022-08
Authors
Kim, Manse
Johnson, Claire E
Schmalstig, Alan A
Annis, Ayano
Wessel, Sarah E
Van Horn, Brian
Schauer, Amanda
Exner, Agata A
Stout, Jason E
Wahl, Angela
Braunstein, Miriam
Victor Garcia, J
Kovarova, Martina
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(13 total)
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Abstract
Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb) and is a major cause of morbidity and mortality. Successful treatment requires strict adherence to drug regimens for prolonged periods of time. Long-acting (LA) delivery systems have the potential to improve adherence. Here, we show the development of LA injectable drug formulations of the anti-TB drug rifabutin made of biodegradable polymers and biocompatible solvents that solidifies after subcutaneous injection. Addition of amphiphilic compounds increases drug solubility, allowing to significantly increase formulation drug load. Solidified implants have organized microstructures that change with formulation composition. Higher drug load results in smaller pore size that alters implant erosion and allows sustained drug release. The translational relevance of these observations in BALB/c mice is demonstrated by (1) delivering high plasma drug concentrations for 16 weeks, (2) preventing acquisition of Mtb infection, and (3) clearing acute Mtb infection from the lung and other tissues.
Type
Journal article
Subject
Animals
Mice
Mycobacterium tuberculosis
Tuberculosis
Rifabutin
Antitubercular Agents
Drug Delivery Systems
Permalink
https://hdl.handle.net/10161/26257
Published Version (Please cite this version)
10.1038/s41467-022-32043-3
Publication Info
Kim, Manse; Johnson, Claire E; Schmalstig, Alan A; Annis, Ayano; Wessel, Sarah E; Van Horn, Brian; ... Kovarova, Martina (2022). A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis. Nature communications, 13(1). pp. 4455. 10.1038/s41467-022-32043-3. Retrieved from https://hdl.handle.net/10161/26257.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Stout

Jason Eric Stout

Professor of Medicine
My research focuses on the epidemiology, natural history, and treatment of tuberculosis and nontuberculous mycobacterial infections. I am also interested in the impact of HIV infection on mycobacterial infection and disease, and in examining health disparities as they relate to infectious diseases, particularly in immigrant populations.
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