pH-responsive ion release kinetics of a chitosan-based hydrogel incorporating nanohydroxyapatite and sodium fluoride for enamel remineralization

BACKGROUND: Ion-releasing dental varnishes vary in composition and pH responsiveness, influencing remineralization efficacy. This study aimed to compare pH-responsive multi-ion release profiles of (1) sodium fluoride (NaF) varnish, (2) casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)/NaF varnish, and (3) a newly synthesized NaF/nanohydroxyapatite (nHA)‑loaded chitosan (CS) hydrogel. METHODS: Seventy-two sound primary canine specimens were prepared with standardized enamel windows and allocated to eight groups (n = 9) by material and buffer pH (5.5 or 7.0). Test materials included NaF varnish, CPP-ACP/NaF varnish, and experimentally formulated NaF/nHA-loaded CS hydrogel. Samples were individually immersed in buffer solutions at pH 5.5 and pH 7.0. Solutions were renewed at 4, 24, 72, and 168 h, and analyzed by ion chromatography for fluoride, phosphate, and calcium concentrations. pH stability was monitored. Data were evaluated by 3-way repeated measures ANOVA and one-way ANOVA with Tukey's post hoc (p < 0.05). RESULTS: At pH 5.5, CPP-ACP/NaF varnish yielded the highest cumulative fluoride release with peak fluoride output in the first four hours (22.40 ± 0.23 ppm). NaF/nHA-loaded CS hydrogel exhibited the highest calcium release in the first four hours (11.40 ± 0.20 ppm) and sustained both calcium (30.20 ± 0.20 ppm) and phosphate (36.20 ± 0.20 ppm) through 168 h. Phosphate release peaked at 24 h for both the NaF/nHA-loaded CS hydrogel and the CPP-ACP/NaF varnish under both pH conditions. At pH 7.0, all ion releases were significantly reduced (p < 0.001), though relative material rankings remained the same. Buffer pH remained stable throughout (p > 0.05). CONCLUSION: While CPP-ACP/NaF varnish maximized early fluoride output, the NaF/nHA-loaded CS hydrogel demonstrated the most sustained multi-ion release under acidic conditions. These distinct pH-dependent kinetics suggest rapid fluoride delivery for early lesion resistance and sustained multi-ion release for extended remineralization.