Liposomal Nanocarriers for Tuberculosis Therapy: Design, Challenges, and Clinical Translation

Abstract

AbstractTuberculosis (TB) remains one of the leading infectious causes of death globally, withMycobacterium tuberculosis infecting an estimated 10.6 million people in 2022 and claiming 1.3million lives. The emergence of multidrug-resistant (MDR-TB) and extensively drug-resistant(XDR-TB) strains has critically undermined first-line chemotherapy regimens. Conventional anti-TBdrugs suffer from poor bioavailability, hepatotoxicity, subtherapeutic concentrations at the site ofinfection, and long treatment durations that drive non-compliance. Liposomal nanocarriers haveemerged as a compelling solution, offering macrophage-targeted drug delivery, intracellular drugaccumulation within Mycobacterium-harboring phagosomes, reduced systemic toxicity, andpotential for dose reduction. This review systematically examines liposomal formulation strategiesfor anti-TB drugs, including rifampicin, isoniazid, pyrazinamide, bedaquiline, and capreomycin,with data drawn exclusively from published research. We analyze in vitro macrophage uptakestudies, in vivo efficacy, and pharmacokinetic data in murine and guinea pig aerosol infectionmodels, and evaluate the gap between preclinical promise and clinical translation. Regulatoryrequirements, GMP scale-up barriers, and the economic constraints of deploying advanced drugdelivery systems in high-burden, low-income settings are critically discussed. Future directionsinclude mannose-receptor-targeted liposomes, inhalable pulmonary formulations, and AI-assistedformulation optimization.