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.