Nanomedicines for the treatment of tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) is the bacterium responsible for the human disease tuberculosis (TB). This study aimed to develop a rapid, low cost assay for screening the anti-mycobacterial properties of new therapies. This assay employed a Green Fluorescent Protein reporter strain of Mycobacteruim avium subspecies paratuberculosis (Map), a pathogenic species causing paratuberculosis in ruminants that can be considered a model for Mtb. Mycobacterial growth over time was monitored by fluorescence, testing new potential therapies including metal and drug nanoparticles (NPs), over a range of concentrations for up to 7 days. The new Map-based assay was sufficiently sensitive to distinguish between the toxicity of different metal/metal oxide NPs, ranked: Ag>Cu(II)O>ZnO. Solid drug NPs (SDNs) of TB antibiotics (rifampicin, isoniazid and pyrazinamide) were compared to conventional antibiotics. SDNs of rifampicin were found to be 100 times more toxic to Map than the conventional antibiotics. Fluorescence microscopy revealed the uptake of SDNs by infected macrophages with possible co-localisation with Map. Pilot data supports the ability of the SDN to kill the intracellular Map. These results support the benefits of nanomedicine and suggest that drug doses could be reduced, if delivered as a nano-formulation.