A Nanoengineered Macrophage-Selective Drug Delivery Platform for Tuberculosis Therapy: Integration of Molecular Docking, Computational Screening, and In-Vivo Evaluation
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Abstract
Tuberculosis continues to pose a serious global health problem, largely because antitubercular drugs show limited penetration into macrophages, the primary host cells of Mycobacterium tuberculosis. This study combines molecular docking and nanoengineering approaches to develop a macrophage-targeted drug delivery system for improved intracellular drug delivery and therapeutic efficiency. Docking analysis indicated strong interactions between rifampicin and the PLGA polymer, supporting its selection for nanoparticle formulation. The nanoformulation optimized using a Box–Behnken design displayed suitable nanoscale size, high drug entrapment, and controlled release properties. In-vitro studies confirmed enhanced macrophage uptake and improved antimicrobial activity compared with the free drug. In-vivo evaluations demonstrated prolonged drug circulation, higher bioavailability, reduced hepatotoxicity, and significant reduction of bacterial load in infected tissues. Overall, the findings highlight the potential of this computationally guided nanoformulation as an effective strategy for targeted tuberculosis therapy.
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References
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