Supramolecular Adenosine–Ectoine Complex for Enhanced Skin Delivery and Anti-Aging Efficacy

Skin aging is a central focus of skin health. Supramolecular chemistry has emerged as a powerful strategy for enhancing the performance of cosmetic active ingredients. Adenosine is a promising anti-aging ingredient in skincare products, but its cosmetic application is limited by poor water solubility and low skin penetration. This study developed a supramolecular complex combining adenosine with ectoine through cocrystallization. The supramolecular assembly was characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculations revealed extensive hydrogen-bonding networks between the components. The optimal supramolecular composition (1:1.5 molar ratio) achieved a 5.5-fold increase in water solubility. The supramolecular organization enhanced skin permeability by 3.1-fold in ex vivo porcine skin models. In fibroblast cell models, the supramolecular system exhibited superior antioxidant activity with 30.3% greater reactive oxygen species (ROS) reduction and restored cellular adenosine triphosphate (ATP) levels by 2.1-fold under H2O2-induced oxidative stress compared to individual components. These findings demonstrate that the adenosine–ectoine supramolecular complex represents an innovative multifunctional ingredient for basic anti-aging cosmetics, offering enhanced delivery, improved safety, and superior biological efficacy through supramolecular engineering.