Dual pH and temperature -responsive hydrogel delivery system containing “intelligent particles” for the treatment of dental caries: an in vitro study

Objective: To investigate a pH and temperature -responsive formulation for targeted antibiofilm activity and silver ion release under cariogenic conditions. Methods: The formulation was prepared by simple physical blending. Microstructural features of the lyophilised formulation were examined using TEM and EDX. Thermo -responsive gelation was evaluated by dynamic viscosity analysis and the tube inversion method. pH -responsive silver ion release was measured at pH 4 and 7. Antibiofilm activity was assessed against a multispecies oral biofilm grown on hydroxyapatite discs using an in vitro flow cell system, with analysis by CLSM, SEM, and CFU counts. Cytotoxicity and inflammatory response were evaluated in human gingival fibroblasts and differentiated THP-1 cells. Results: The lyophilised formulation exhibited a multi-layer, highly porous interconnected network with confirmed IPs incorporation. It transitioned from solution to gel within 1 minute at 36°C. Silver ion release was pH -dependent, showing a rapid burst release at pH 4 (91.40 ± 4.98%), significantly (p <0.0001) greater than at pH 7 (58.28 ± 0.67%). The formulation disrupted biofilms and inhibited bacterial growth by 2-Log (p < 0.001) under acidic conditions at an Ag⁺ concentration of 0.93 µg/mL. Cytotoxicity and inflammation assays confirmed the antibiofilm concentration was non-toxic and did not trigger an inflammatory response. Conclusion: The formulation demonstrates strong potential for targeted treatment and prevention of dental caries through controlled silver ion release and effective antibiofilm activity without compromising biocompatibility. Clinical Significance: Dental caries remains a major oral health challenge requiring new therapeutic approaches. This dual -responsive formulation offers a promising shift in caries prevention and treatment, with clear potential for commercial development and future clinical translation.