A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 08 2022
08 08 2022
Historique:
received:
11
02
2022
accepted:
14
07
2022
entrez:
8
8
2022
pubmed:
9
8
2022
medline:
11
8
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35941109
doi: 10.1038/s41467-022-32043-3
pii: 10.1038/s41467-022-32043-3
pmc: PMC9360445
doi:
Substances chimiques
Antitubercular Agents
0
Rifabutin
1W306TDA6S
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4455Subventions
Organisme : NIAID NIH HHS
ID : R01 AI123010
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140799
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Informations de copyright
© 2022. The Author(s).
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