Effective resistance to UVB-induced skin damage through the encapsulation of chebulinic acid in mulberry-derived exosome‐like nanoparticles

Ultraviolet-B (UVB) radiation induces significant skin damage by penetrating into the dermal layer, leading to reactive oxygen species (ROS) generation and triggering cellular necrosis and apoptosis. Conventional sunscreens focus primarily on UVB blocking but are limited in their ability to repair dermal damage due to insufficient permeability. In this study, we discover that chebulinic acid (CA), one of the principal monomers in <i>Terminalia chebula</i> Retz., has superior efficacy in promoting recovery from UVB-induced skin damage compared with other major monomers. Mechanistically, CA's anti-UVB function involves regulating the expression of IL-6 and IFN-β through activation of the MAPK pathway. To overcome the formidable barrier posed by the skin, we identify mulberry exosome-like nanoparticles (MELNs) as an efficient transdermal delivery system and develop CA@MELNs loaded with CA. Furthermore, we demonstrate that the dissociative CA within the CA@MELNs delivery system significantly enhances both transdermal penetration and anti-UVB efficiency <i>in vitro</i> and <i>in vivo</i>. Our findings suggest the substantial potential of CA as an effective ingredient and CA@MELNs as a robust and accessible platform for mitigating UVB damage.