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A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis.
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 articleSubject
AnimalsMice
Mycobacterium tuberculosis
Tuberculosis
Rifabutin
Antitubercular Agents
Drug Delivery Systems
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https://hdl.handle.net/10161/26257Published Version (Please cite this version)
10.1038/s41467-022-32043-3Publication 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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Show full item recordScholars@Duke
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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