Advancing Tuberculosis Chemotherapy: Targeted Nanomedicines for the Mycobacterium TB Granuloma.

This review examines the potential of nanosystems for targeted tuberculosis (TB) therapy, focusing on biodegradable polymeric, lipid-based, extracellular vesicles, and selected inorganic nanocarriers engineered to deliver anti-TB drugs directly to granulomas, the hallmark of TB pathology. Both passive and active targeting strategies are discussed, emphasizing how these approaches enhance drug accumulation at infection sites to curb disease progression. Preclinical studies, including laboratory and animal models, are reviewed to assess their therapeutic impact. Although the results are promising, hurdles such as biocompatibility, regulatory constraints, and optimizing drug release still pose challenges for clinical implementation. However, rationally designed nanosystems hold significant potential for improving TB treatment outcomes. Further research is crucial for refining nanocarrier design and addressing translational hurdles. Future directions include integrating nanosystems with advanced molecular imprinting technologies (MIT) and molecularly imprinted polymer nanoparticles (MIPNPs) for enhanced granuloma targeting and controlled drug release. Additionally, immunotherapy and gene therapy offer novel adjunct strategies to boost host immunity and deliver targeted genetic interventions. These emerging approaches, combined with optimized nanosystems, have the potential to revolutionize TB management by improving drug delivery, reducing treatment duration, and enhancing therapeutic outcomes.