Antimycobacterial and autophagic activity of nebulized delamanid microemulsion targeting alveolar macrophage.

Abstract

Objective: The aerosol delivery of the novel anti-tubercular drug delamanid for pulmonary targeting holds promise for the effective treatment of multi-drug-resistant tuberculosis. Here, we developed a microemulsion formulation of delamanid for nebulization, evaluating its potential bioactivity.

Methods: Herein, we attempted to develop microemulsion formulations loaded delamanid for nebulization and their physicochemical characteristics were assessed. The formulation was checked for aerosol characteristics, cytotoxic potential, in vitro antimycobacterial activity, and autophagy.

Results: The optimized formulations, nebulized into a next-generation impactor, exhibited a fine particle fraction of 63.12%, ensuring efficient in vitro deposition. In vitro evaluations revealed that formulation did not demonstrate any cytotoxic potential on respiratory cell lines up to 2.5 µg/mL and lack of inflammatory cytokines production and nitric oxide from macrophage NR8383 cells, signified its safety. The flow cytometry analysis revealed that the elimination of Mycobacterium bovis by formulation after day 4, with considerably low minimum bactericidal concentration. The formulation demonstrated adequate macrophage autophagic activity when evaluated using confocal laser scanning microscopy and Western blot.

Conclusion: Consequently, the aerosolized microemulsion of delamanid for pulmonary delivery may serve as an effective therapy for MDR-TB, necessitating further in vivo studies.