Nanomedicine-based drug delivery systems for tuberculosis: Overcoming resistance, dormancy, and translational barriers

Tuberculosis continues to pose a serious global health threat, even after many years of substantial investment in treatment research and development. According to the World Health Organization, around 10.7 million new cases occurred in 2024, causing 1.23 million deaths. The clinical challenge of tuberculosis is intensified by its ability to remain dormant, the rise of highly resistant MDR and XDR strains, and the inherent flaws of current treatment, including high toxicity and poor absorption. These factors necessitate the immediate development of more advanced delivery systems and therapeutic interventions. This review emphasizes the recent advancement in nanomedicine-based drug delivery systems for TB treatment and assesses their ability to overcome the principal pharmacological and biological barriers. Various nanocarriers, including liposomes, niosomes, polymeric nanoparticles, dendrimers, solid-lipid nanoparticles, nanoemulsions, and carbon nanotubes, are discussed for their ability to enhance drug solubility, stability, controlled release, and targeted intracellular delivery. A central focus of this discussion is the capacity of nanocarriers to circumvent resistance pathways, specifically efflux pump inhibition and protection against enzymatic breakdown. Furthermore, we analyse how these systems enhance deep penetration into tuberculosis granulomas to effectively reach dormant mycobacteria and specific macrophage subsets. Beyond mechanical advantages, this review evaluates the pharmacokinetic profiles and safety margins of leading nanocarriers. We evaluate the current clinical landscape, including active trials and patented technologies, while critically addressing the translational hurdles of scalability and cost. Finally, we provide a strategic outlook on bridging the gap between nanomedicine innovation and its practical implementation in high-burden, resource-limited settings.