Modulation of Piceatannol Skin Diffusion by Spilanthol and UV Filters: Insights from the Strat-M™ Model

Background: currently, there is a growing trend toward multifunctional cosmetics, which combine several active ingredients in a single product to enhance efficacy and user convenience. As ingredients may influence one another, it is important to study the behavior of mixing multiple compounds in complex formulations, especially regarding their interaction with the skin. Piceatannol, for instance, is a naturally occurring stilbene recognized for its in vitro potent antioxidant, anti-inflammatory, and anti-aging activities, making it a promising candidate for dermocosmetic use in suncare. But despite its beneficial biological activities, its cutaneous permeation remains poorly understood, particularly when delivered from complex formulations containing multiple ingredients. Objectives: in this sense, this study aimed to evaluate the in vitro skin diffusion profile of piceatannol from a passion fruit seed extract (Pext) incorporated into a topical base (Bem) or an organic sunscreen emulsion (Oem), with or without a spilanthol-rich Acmella oleracea extract (Jext) used as a natural permeation enhancer. Methods: due to ethical and variability issues with human and animal skins, the Strat-M™ synthetic membrane was chosen as a standardized model for the in vitro skin permeation assays. Piceatannol localization within membrane layers was examined by confocal Raman microscopy (CRM), while compound identification in donor and receptor compartments was performed via UHPLC-DAD. Results: piceatannol from Bem was detected up to 140 µm from the Strat-M™ surface and exceeded 180 µm in depth when Jext and organic sunscreens were included in the formulation. Notably, formulations containing Jext and those based on Oem promoted enhanced accumulation in both the stratum corneum and deeper skin layers, suggesting an improved delivery potential in lipid-rich vehicles. Conclusions: even though some instability issues were observed, piceatannol penetration into Strat-M™ from the proposed formulations was confirmed, and the results provide a foundation for further research on its topical delivery, supporting the rational development of formulations capable of harnessing its demonstrated biological properties.