Safety-constrained evaluation of antibacterial multicomponent borate glasses.

Soluble ion-releasing materials intended for transient, dilution-limited use must achieve functional performance while maintaining safety under repeated exposure. This study presents a clinically parameterized framework for the design of multi-ion, soluble glasses for toothpaste applications by integrating a Design-of-Mixtures composition space with brushing-relevant extraction conditions. Glasses within a constrained Ag2O-NaF-CaO design domain were synthesized, characterized, and evaluated using 2 min aqueous extracts to quantify dissolution behavior, multi-element ion release, and antibacterial activity against Streptococcus mutans at clinically plausible dilutions. By maintaining a constant extraction ratio across the mixture space, compositional effects on early-time dissolution and ion speciation were isolated under exposure conditions relevant to transient plaque pH challenges. Composition-response modeling demonstrated that calcium release establishes a thermodynamically constrained, remineralization-relevant baseline, whereas silver-mediated antibacterial activity is non-monotonic and highly composition-dependent, indicating that antibacterial potency can be engineered through controlled dissolution rather than increased silver loading. Ag2O-NaF interaction effects consistent with speciation-sensitive co-release were identified, supporting strategies that preserve fluoride availability while optimizing antimicrobial performance. An ISO 10993-17-aligned toxicological risk assessment was applied as a conservative, exposure-based screening tool to map efficacy-safety relationships across the design space and prioritize dose-efficient compositions. Together, this workflow provides a safety-constrained framework for evaluating antibacterial ion-releasing glasses and for assessing transient, multi-ion delivery materials under realistic exposure conditions.