Multi-metallic microparticles for the treatment of pulmonary tuberculosis

Mycobacterium tuberculosis (M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics. In this work, biodegradable multi-metallic microparticles (MMPs), containing Ag and ZnO NPs, were developed for use in the pulmonary delivery of antituberculous drugs to the endosomal system of M.tb-infected macrophages. Ag NPs were synthesised with a uniform size distribution, having a mean diameter of 15 nm; well suited for potent antitubercular activity against M.tb. ZnO NPs were successfully synthesised with a smaller mean diameter of 4 nm, providing NPs with a large surface area to volume ratio. ZnO NPs, with a large surface area to volume ratio, act as potent antimicrobials through direct NP interaction ... (continues)