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

Author

Listed:
  • Manse Kim

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Claire E. Johnson

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Alan A. Schmalstig

    (University of North Carolina at Chapel Hill)

  • Ayano Annis

    (University of North Carolina at Chapel Hill)

  • Sarah E. Wessel

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Brian Horn

    (University of North Carolina at Chapel Hill)

  • Amanda Schauer

    (University of North Carolina at Chapel Hill)

  • Agata A. Exner

    (Case Western Reserve University)

  • Jason E. Stout

    (Duke University)

  • Angela Wahl

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Miriam Braunstein

    (University of North Carolina at Chapel Hill)

  • J. Victor Garcia

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Martina Kovarova

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

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.

Suggested Citation

  • Manse Kim & Claire E. Johnson & Alan A. Schmalstig & Ayano Annis & Sarah E. Wessel & Brian Horn & Amanda Schauer & Agata A. Exner & Jason E. Stout & Angela Wahl & Miriam Braunstein & J. Victor Garcia , 2022. "A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32043-3
    DOI: 10.1038/s41467-022-32043-3
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    References listed on IDEAS

    as
    1. Martina Kovarova & S. Rahima Benhabbour & Ivana Massud & Rae Ann Spagnuolo & Brianna Skinner & Caroline E. Baker & Craig Sykes & Katie R. Mollan & Angela D. M. Kashuba & J. Gerardo García-Lerma & Russ, 2018. "Ultra-long-acting removable drug delivery system for HIV treatment and prevention," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    2. Abriham Zegeye & Getnet Dessie & Fasil Wagnew & Alemu Gebrie & Sheikh Mohammed Shariful Islam & Bekele Tesfaye & Dessalegn Kiross, 2019. "Prevalence and determinants of anti-tuberculosis treatment non-adherence in Ethiopia: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 14(1), pages 1-15, January.
    3. S. Rahima Benhabbour & Martina Kovarova & Clinton Jones & Daijha J. Copeland & Roopali Shrivastava & Michael D. Swanson & Craig Sykes & Phong T. Ho & Mackenzie L. Cottrell & Anush Sridharan & Samantha, 2019. "Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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