Co-Delivery Systems of Antibiotics for Combating Resistant Forms of Tuberculosis

Abstract Current approaches to the development of co-delivery systems for two or more active agents for the therapy of tuberculosis are systematized. The physicochemical properties of key anti-tuberculosis drugs (bedaquiline, pretomanid, linezolid, moxifloxacin, delamanid, clofazimine) that determine the choice of carrier are reviewed. The main types of nanocarriers for co-delivery are analyzed: functionalized liposomes, polymeric nanoparticles, metal-organic frameworks, and hybrid systems with spatial separation of drugs. Mechanisms for combating resistant forms of tuberculosis using co-delivery are discussed, including synergistic action, modulation of the infection microenvironment, and optimization of pharmacokinetics. Particular attention is paid to combinations of antibiotics with antimicrobial peptides, adjuvants (flavonoids, essential oils, vitamins, efflux pump inhibitors), and unconventional agents (nitric oxide donors, fluoxetine, bacteriophage enzymes). It is shown that co-delivery systems provide synergistic action, multiple reduction of minimum inhibitory concentration, prolonged release, and the possibility of reducing dosing frequency to once weekly. Key barriers to clinical translation (scalability, standardization, toxicity, regulatory challenges) are identified, and promising frontiers are outlined: smart systems responsive to the microenvironment, use of artificial intelligence for predicting optimal combinations, fully biodegradable MOFs, and co-delivery of three or more agents with different mechanisms of action.