Metal-organic framework-based drug delivery for treatment of tuberculosis

Abstract

Tuberculosis (TB) is globally recognized as the second most fatal disease after HIV and AIDS. Due to the multi-drug resistant (MDR) and extensively drug- resistant (XDR) properties of M. tuberculosis, it is becoming difficult to treat the patients. Major drawbacks of already available antibiotics for TB treatment are high dose administration, poor bioavailability, and low biodegradability. To overcome this problem, we tried to develop a novel drug delivery system that would deliver the drug specifically to the infected macrophages. In this work, we have encapsulated the well-known first-line anti-TB drug Rifampin (RIF) into the Zeolitic Imidazole Framework (ZIF-8). Successful encapsulation of Rifampin into ZIF-8 was confirmed by different characterization techniques such as UV-Vis spectroscopy, FT-IR, TGA, TEM, SEM, BET analysis and PXRD. Further pH-responsive drug release and fluorescence studies and reduced cell cytotoxicity confirm that RIF- loaded ZIF-8 can be treated as a suitable candidate for the delivery of anti- tubercular agents and reveal the potential application for tuberculosis treatment. Overall, this thesis contributes to the burgeoning field of MOF- based drug delivery systems, offering valuable insights into their application for TB treatment. The findings underscore the promising potential of ZIF-8 as a versatile platform for the controlled delivery of anti-TB drugs, paving the way for future advancements in targeted therapeutic interventions against tuberculosis. Keywords: Metal-organic framework, tuberculosis, rifampicin, ZIF-8, drug delivery, cytotoxicity, cellular uptake, pH-responsive release.