Microenvironment-sensitive hydrogels as promising drug delivery systems for co-encapsulating microbial homeostasis probiotics and anti-inflammatory drugs to treat periodontitis

Developing and utilizing effective local antimicrobial agents can help treat periodontitis while minimizing the risks associated with systemic antibiotic use. Recent studies have shown that the mucosal adhesion properties of hydrogels can play a potential role in the treatment of periodontitis. The hydrogel can improve the contact and retention time of drugs in the periodontal pocket. Through the adhesion of mucosa, it interacts with the mucin coating surface of epithelium and teeth to form a specific interface force. The hydrogel exhibits strong mucosal adhesion (adhesion strength: 5–6 N/cm2) and prolonged retention in periodontal pockets (≥6 h), enabling sustained drug release through dynamic sol-gel transitions triggered by pH and reactive oxygen species (ROS). This design overcomes the limitations of poor mechanical stability in conventional formulations. The dynamic balance of oral microbiota plays an important role in maintaining oral health. Probiotics, by colonizing the oral cavity, transform the infected site from an environment rich in inflammatory cytokines to a more benign environment, inhibit harmful pathogenic microorganisms, and contribute to overall health. Microenvironment sensitive hydrogels can perform dynamic sol gel transformation in situ, and can accurately control drug release when exposed to various stimuli (such as temperature change, light, pH change, reactive oxygen species, etc.). Oral probiotics and anti-inflammatory drugs are encapsulated in hydrogels to inhibit the proliferation and adhesion of oral pathogens by planting in the mouth and producing metabolites, effectively preventing and treating oral diseases.