Preparation and Characterization of an Acid-Responsive ZIF-8 Hydrogel Dressing with Sustained-Release Function for Targeted Therapy of Periodontitis

Periodontitis is a chronic oral inflammatory disease whose treatment is often hindered by poor drug retention, prolonged therapeutic regimens, and the rise of antibiotic resistance. In this study, we developed a Hydrogel@ZIF-8@metronidazole (Hydrogel@ZIF-8@MNZ) nanocomposite dressing for targeted, sustained, and in situ antimicrobial therapy. This system integrates ZIF-8, a pH-responsive metal-organic framework, with the antimicrobial agent metronidazole (MNZ), encapsulated within a crosslinked hydrogel matrix to enhance stability and retention in the oral environment. Drug release studies demonstrated that MNZ release was significantly accelerated under acidic conditions (pH 5.0), mimicking the periodontal microenvironment. The Hydrogel@ZIF-8 composite achieved a maximum MNZ adsorption capacity of 132.45 mg·g^-1, with a spontaneous and exothermic uptake process best described by a pseudo-second-order kinetic model, suggesting chemisorption as the dominant mechanism. The nanoplatform exhibited strong pH-responsive behavior, with enhanced drug release under acidic conditions and potent dose-dependent bactericidal activity against Fusobacterium nucleatum (Fn). At the highest tested concentration, bacterial survival was reduced to approximately 30%, with extensive membrane disruption observed through live/dead fluorescence microscopy. In summary, the stimuli-responsive Hydrogel@ZIF-8@MNZ nanocomposite offers an intelligent and effective therapeutic strategy for periodontitis. By tailoring its action to the disease microenvironment, this platform enables sustained and localized antibacterial therapy, addressing major challenges in the treatment of chronic oral infections.