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. <i>In vitro</i> 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 <i>Pseudomonas aeruginosa</i> 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.