Harnessing silver nanoparticles with pretomanid for enhanced antimycobacterial therapy

The emergence of Multidrug-Resistant Mycobacterium Tuberculosis (MDR-TB) necessitates the development of novel therapeutic strategies to enhance antimycobacterial efficacy. This work explores the potential synergy between Silver Nanoparticles (AgNPs) and Pretomanid, a novel nitroimidazo-oxazine anti-TB agent, to improve drug distribution and bactericidal action. AgNPs were produced using a green chemical reduction technique, and they were subsequently loaded with Pretomanid to form a stable nanosystem. The nanoconjugates were examined using Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). SEM investigation showed mostly spherical nanoparticles with sizes between 15 and 25nm, a homogeneous dispersion, and little aggregation. Pretomanid's internalization within the AgNP matrix was verified by TEM imaging, which also showed distinct electron-dense cores, signifying effective drug loading and stable encapsulation. Increased surface area, which is essential for contact with mycobacterial cells, was suggested by the surface morphology. AgNP-Pretomanid conjugates showed far more inhibitory efficacy against the M. tuberculosis H37Rv strain than free Pretomanid, with A Minimum Inhibitory Concentration (MIC) reduction of about 40%, according to in vitro antimycobacterial studies. The enhanced effectiveness is caused by two mechanisms of action: premanid-induced respiratory inhibition in hypoxic environments and silver-mediated bacterial cell membrane disruption. Cytotoxicity tests on human macrophage cell lines confirmed the biocompatibility of the nanoconjugates at therapeutically relevant concentrations. This study highlights the potential of AgNP-based drug delivery systems to boost the efficacy of currently available anti-TB medications. The importance of nanoparticles in enhanced antimycobacterial activity was confirmed by SEM and TEM studies, which provided vital information about their size distribution, shape, and drug loading effectiveness. All things considered, by improving drug delivery and generating synergistic antibacterial effects, the AgNP-Pretomanid nanoconjugates present a possible treatment approach for drug-resistant tuberculosis.

Keywords: Silver Nanoparticles, Pretomanid, Antimycobacterial Therapy, Cytotoxicity, Stability.

Nitasha Pathak Joshi is an experienced pharmaceutical professional with over ten years of expertise in drug discovery, regulatory compliance, and analytical research. She holds an M.Pharm in Drug Discovery and is currently working as a Research Scientist at the Indian Pharmacopeia Commission, Ghaziabad. Her work includes regulatory document review, analytical method validation, stability studies, and handling advanced instruments such as HPLC and LC–MS. She has led major regulatory audits and training programs and is recognized for her strong analytical, leadership, and compliance-oriented approach.