Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat
infections. To increase efficacy of pulmonary treatment of mycobacterial
infections an inhalable
antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight
sodium hyaluronate sub-micron particles were efficiently loaded with
rifampicin,
isoniazid and
verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the
powder was characterized by a slow release rate, favorable to maintain a high
drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage
infection assays employing susceptible and
drug resistant strains were carried out. No significant differences were observed when the
powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without
verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial
respiratory infections, regardless the level of drug resistance.