Synergistic combination: Developing a natural carrier-free assembled gel through hydrogen bond reconstruction...

The risk of developing melanoma from long-term exposure to UVB has drawn public attention to ultraviolet protection and post-sun repair. Increasing evidence has demonstrated that the outbreak of oxidative stress and inflammation is a major cause of skin photodamage. The potential for natural flavonoids to repair and defend against skin photodamage makes them a valuable asset, but their low solubility and bioavailability limits their practical applications. Herein, we report a novel natural carrier-free assembled gel, composed of natural moisturizing factor sodium pyrrolidone carboxylate (PCA-Na) and insoluble small-molecule baicalin (BA), for the repair of skin photodamage. This gel features a simple preparation method, which involves dispersing BA in water and then adding PCA-Na as part of the solvent. The best way to obtain a clear solution is to stir uniformly at a low temperature (45 °C). The carrier-free assembled gel (BP-Gel) can be easily formed by allowing the solution to stand at 4 °C. PCA-Na enhances the solubility of BA and induces the assembly of BA into a gel primarily by breaking the intramolecular hydrogen bonds of BA and reconstructing an intermolecular hydrogen bond network. In vitro experiments showed that BP-Gel can scavenge reactive oxygen species (ROS), protect mitochondria and shield cells from oxidative damage, as well as alleviating inflammation. Further in vivo experiments confirmed that BP-Gel effectively alleviates UVB-induced skin photodamage by restoring oxidative homeostasis in vivo, inhibiting inflammatory responses and regulating collagen-related proteins. In conclusion, the powerful combination of natural moisturizing factors and plant-derived natural flavonoids provides a green, economical, and highly feasible strategy for the development of drugs for antioxidant- and anti-inflammatory-related skin diseases, and it also indicates broad prospects for the development of drugs derived from natural renewable resources.