Surface immobilization of antimicrobial parabens on TiO₂ nanoparticles for reduced dermal absorption risk

Parabens are widely used preservatives in cosmetics and pharmaceuticals due to strong antimicrobial activity and cost-effectiveness. However, concerns about their potential endocrine-disrupting effects have led to regulatory restrictions in several countries. In this study, we present a strategy to immobilize parabens on TiO₂ nanoparticles—commonly used as UV-blocking agents— to retain preservative efficacy while minimizing dermal absorption. To achieve efficient immobilization of parabens, three linker molecules bearing functional groups capable of binding both TiO₂ and parabens were selected. The adsorption of these linkers onto the TiO₂ surface was confirmed by zeta potential analysis and Fourier-transform infrared spectroscopy, and their loading was quantified using thermogravimetric analysis. Quantitative analysis using high-performance liquid chromatography showed paraben adsorption up to 160% higher on functionalized particles than on pristine TiO₂ particles. In vitro cytotoxicity assays using human dermal fibroblasts demonstrated minimal toxicity of the paraben-immobilized TiO₂ particles (PiPs). Furthermore, antibacterial tests against Staphylococcus aureus demonstrated enhanced antimicrobial activity of the PiPs, attributed to increased loading facilitated by the linker molecules. These results indicate that the proposed paraben-immobilized nanoparticle system offers a promising route for effective preservation with reduced dermal absorption.