ZIF-8@ceftazidime nanocomposite for the treatment of Pseudomonas aeruginosa–induced urinary tract infection

Complicated urinary tract infections (UTIs) caused by Pseudomonas aeruginosa are difficult to treat due to biofilm-mediated resistance and the limitations of conventional antibiotics like ceftazidime (CAZ). To address this challenge, a nanotherapeutic system, ZIF-8@CAZ, was developed by encapsulating CAZ within a zeolitic imidazolate framework-8 (ZIF-8) nanocarrier. This nanocomposite exhibited sustained drug release and significantly enhanced in vitro antibacterial efficacy against P. aeruginosa PAO1, as evidenced by a substantially lower minimum inhibitory concentration compared to free CAZ, along with potent anti-biofilm activity. In a murine model of ascending UTI, ZIF-8@CAZ treatment resulted in a dramatic reduction of bacterial burden in bladder tissues, significant attenuation of inflammation (as shown by decreased levels of IL-6 and TNF-α), and superior amelioration of tissue pathology compared to an equivalent dose of free CAZ. Furthermore, comprehensive biosafety evaluations confirmed the excellent biocompatibility of ZIF-8@CAZ, with no observed systemic toxicity. These findings demonstrate that ZIF-8@CAZ is a promising nanoplatform for the effective treatment of biofilm-associated UTIs.