A Supramolecular System of Bioactive Ionic Liquid, Peony Extract, and Peptide for Enhanced Permeability and Synergistic Skincare Benefits

The growing demand for safe and sustainable cosmetics has led to a marked inclination toward natural extracts and peptides as raw materials. In this study, we developed a sustainable system with multiple antiaging effects by combining peony extract (PE) and acetyl hexapeptide-8 (AHP8) to simultaneously treat static and dynamic wrinkles, as well as skin dullness. As the poor skin permeability of AHP8 limited its efficacy, we used a bioactive ionic liquid derived from betaine and malic acid (MA) ([Bet][MA]) as a permeation enhancer. In vitro and in vivo zebrafish experiments indicated that [Bet][MA] not only significantly enhances transdermal and cellular penetration, but also exerts synergistic anti-aging effects. While being biosafe, [Bet][MA] significantly increased the transdermal permeation, skin retention, and cellular uptake of AHP8. Theoretical calculations revealed that [Bet][MA] improved the anti-wrinkle and whitening efficacies of AHP8 and PE through supramolecular interactions; it modulated their electron cloud distribution and molecular polarity and thus intensified their affinity to target proteins. The supramolecular PE/AHP8/[Bet][MA] system demonstrated excellent radical- and reactive oxygen species-scavenging capability, collagen production, and tissue repair capability while concurrently inhibiting tyrosinase activity, motion signaling, and inflammation. The study findings pave the way for sustainable and multifunctional skincare solutions.