Co-delivery of loaded 4-butylresorcinol and licochalcone A in a supramolecular system for synergistic permeation and whitening effects

As people age and are exposed to the sunlight for a long time, the excessive production and accumulation of melanin in the skin can affect their appearance and health. In addition, some whitening active ingredients have limitations in terms of solubility, stability, and skin irritation, which prompted us to research more effective techniques to improve the skincare effects of active ingredients. 4-Butylresorcinol (BR) can achieve whitening by inhibiting the activity of tyrosinase (TYR) and dihydroxyindole carboxylate oxidase. However, the high irritancy of BR limits its application. Therefore, we prepared supramolecular BR–LicoA–VE by intermolecular forces from BR, licoricarketone A (LicoA), and vitamin E acetate (VE). Compared with single BR, supramolecular BR–LicoA–VE exhibits good skin permeability and stability at room temperature, significantly reduces skin melanin content (30.55%), and inhibits the activity of TYR (59.90%). Through simulation calculations, it was found that supramolecular BR–LicoA–VE can inhibit the production of melanin in cells by suppressing the expression of melanin-related proteins such as TYR, endothelin-1, mammalian target of rapamycin, and microphthalmia-associated transcription factor. In the human experiments, a formula containing supramolecular BR–LicoA–VE shows better skin whitening effects after 28 days of use, with the lowest melanin content and the highest whiteness value (increased by 8.95%). Therefore, supramolecular BR–LicoA–VE has potential application value in whitening and skincare.