Bacteria-Responsive Drug Delivery System Utilizing Carboxymethyl Cellulose-Functionalized Metal–Organic Framework for Enhanced Antibacterial Efficacy

Bacterial infections pose a significant threat to human health and economic stability. The overuse of antibiotics has exacerbated bacterial resistance, highlighting the urgent need for innovative strategies to combat this issue. Bacteria-responsive drug delivery systems present a promising solution to overcoming bacterial resistance. Metal–organic frameworks (MOFs), versatile porous materials created by linking metal clusters with organic ligands, are ideal candidates for such applications. Here, we employed the zeolite imidazole framework 8 (ZIF-8) as a carrier for ceftiofur (EFT), enhanced with carboxymethyl cellulose to develop a smart drug delivery system (CMC-EFT@ZIF-8) responsive to pH and cellulase. In vitro tests demonstrated that this system released a higher quantity of EFT under acidic conditions and in the presence of cellulase, leading to more effective disruption of bacterial membranes and subsequent bacterial death. The CMC-EFT@ZIF-8 system achieved a 99% clearance of Pseudomonas aeruginosa within 6 h and showed superior efficacy in a mouse skin wound model. These findings underscore the potential of our smart drug delivery system to significantly improve treatment outcomes for bacterial infections, representing a significant advancement in the fight against antibiotic resistance.