Silybin‐Collagen XVII Composite Nanoemulsion for Enhanced Solubility, Skin Permeation, and Repair of UVB‐Induced Skin Photodamage

Excessive ultraviolet B (UVB) exposure causes oxidative stress, inflammation, barrier disruption, and premature skin aging. Silybin has antioxidant and anti‐inflammatory activity but limited topical delivery because of poor aqueous solubility. Recombinant human type XVII collagen (rhCOL17), which supports hemidesmosome stability, epidermal adhesion, and dermal‐epidermal repair, also requires a suitable carrier for topical use. We developed a silybin‐rhCOL17 composite nanoemulsion and optimized it by response surface methodology. The optimized formulation showed a sub‐100 nm particle size, spherical morphology, good physicochemical stability, 96.91% cumulative silybin release within 24 h under dialysis, and higher transdermal permeation than free silybin. In UVB‐injured HaCaT cells, it improved viability and migration, reduced reactive oxygen species, malondialdehyde, and interleukin‐6, and restored catalase, glutathione, and superoxide dismutase activities. In UVB‐induced mouse skin photodamage, the low‐dose nanoemulsion achieved the best overall repair, improving skin appearance, histopathology, collagen organization, and inflammatory and oxidative stress markers. Mechanistically, silybin mainly provides antioxidant and anti‐inflammatory protection, whereas rhCOL17 likely supports adhesion, barrier repair, and a reparative microenvironment. These findings suggest this composite nanoemulsion is a promising topical strategy for UVB‐induced skin damage.