Enhanced antimycobacterial activity of citrate-capped silver nanoparticles and rifampicin nanoconjugates against Mycobacterium smegmatis

Tuberculosis (TB) remains a significant global health challenge, with a massive burden in densely populated countries like India. Mycobacterium tuberculosis (Mtb) , the causative agent, poses formidable treatment challenges due to its slow growth, latency, and intrinsic drug resistance mechanisms. Although conventional drugs like Isoniazid, Rifampicin, and Ethambutol have shown efficacy against mycobacteria, their prolonged treatment periods demand novel approaches to improve patient compliance and treatment outcomes. Nanoparticles (NPs) like silver nanoparticles (AgNPs) have emerged as promising drug carriers as an alternative approach for TB treatment. AgNPs hold potential as nanocarriers and antimycobacterial agents, especially when combined with rifampicin, a conventional TB drug. In this study, citrate-capped AgNPs were conjugated with rifampicin and evaluated against Mycobacterium smegmatis , a surrogate organism for MTB. The enhanced effects of AgNPs and rifampicin were investigated to enhance rifampicin's efficacy in TB treatment. We observed that prolonged conjugation between AgNPs and rifampicin may allow the nanoconjugate to penetrate bacterial cells more effectively, which in turn could help to overcome certain drug resistance mechanisms . This innovative approach offers a promising avenue for developing an improved drug delivery system for TB treatment, particularly against drug-resistant strains, where conventional therapies have limited success. Schematic representation of AgNP–rifampicin nanoconjugate (AgNP–Rif) formation and its proposed enhanced action on Mycobacterium smegmatis via silver ion release, rifampicin delivery, and ROS generation. • Nanoparticle–rifampicin combo shows promise for TB therapy advancement. • Nanoconjugates show low cytotoxicity and offer dual antimicrobial functionality. • This study lays groundwork for the future nanoparticle-assisted TB therapy and PK/PD evaluations.