Integrating Molecular Docking and Nanoengineering Approaches to Develop a Macrophage-Selective Antitubercular Drug Delivery System: From Computational Prediction to In-Vivo Validation
Keywords:
Molecular docking, macrophage targeting, antitubercular drug delivery, nanoengineering, PLGA nanoparticles, tuberculosis therapy, intracellular deliveryAbstract
Tuberculosis remains a major global health challenge, primarily due to poor drug penetration into macrophages—the intracellular niche of Mycobacterium tuberculosis. This study integrates molecular docking with nanoengineering to design a macrophage-selective drug delivery system that enhances intracellular delivery and therapeutic performance of antitubercular drugs. Molecular docking predicted strong interactions between rifampicin and PLGA polymer, guiding the rational selection of excipients for nanoparticle synthesis. The optimized nanoformulation, engineered through a Box–Behnken design, exhibited favorable physicochemical characteristics including nanoscale size, high entrapment efficiency, and sustained release behavior. In-vitro studies demonstrated enhanced macrophage uptake, efficient intracellular drug retention, and superior antimicrobial activity compared to free drug. In-vivo pharmacokinetic analysis confirmed prolonged circulation, increased bioavailability, and reduced hepatotoxicity. Furthermore, in-vivo efficacy studies revealed a significant reduction in bacterial load in lung and spleen tissues. Overall, this integrated computational-experimental strategy establishes a robust framework for developing advanced macrophage-targeted therapeutics for tuberculosis.
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