Multifunctional System with Ferulic Acid: Increased Safety, Antioxidant Activity, and Efficacy of Sunscreen Formulations

The topical application of ferulic acid (FA) is limited by its low solubility and high susceptibility to oxidation. To overcome these limitations, the multicomponent system Cicloferulic® (CF) was developed by mixing FA, hydroxypropyl β-cyclodextrin (HPβ-CD), and polyvinylpyrrolidone K30 (PVP K30), which demonstrated greater safety and antioxidant efficacy than FA alone. The physicochemical characterization of FA, CF, and their components showed greater thermal stability and reduced crystallinity of CF, indicating the formation of the system. In cytotoxicity assays on HaCaT cells, FA maintained cell viability only up to 500 µg/mL, while CF maintained viability even at 10.000 µg/mL, demonstrating 20 times greater safety than FA. In cellular antioxidant activity assays, FA and CF showed similar effects at low concentrations. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, CF and FA reduced more than 70% of DPPH; however, CF contains only 12% FA, indicating an eightfold greater efficiency than FA. Formulations containing FA and CF increased the Sun Protection Factor (SPF) in vitro, even with a 50% reduction in UV filters. However, they did not stabilize formulations with intrinsically photolabile UV filters. In release studies, FA exhibited rapid flow, while CF promoted a modified release profile. Thus, CF stands out as an innovative, multifunctional system that can improve the stability, safety, and efficacy of FA for topical applications.