Transdermal release behaviors of bioactive deep eutectic solvents as natural skin care and mechanism

This study focused on offering relatively systematic study on transdermal behaviors, bioactivity and mechanism of deep eutectic solvents (DESs) and finding out whether they could be used as a potential natural skin care medium with promoted release performance. A series of new bioactive DESs with potential effects (including 4-methoxy salicylic acid-betaine, lactic acid-betaine, malic acid-betaine, malic acid-choline chloride, malic acid- l -carnitine, mandelic acid-betaine, phytic acid-betaine) were synthesized and their permeation behaviors were all investigated by using bionic and mice skins. It showed that the transdermal releasing process could be mainly controlled by both concentration and viscosity of specific DESs, and 1000 mg/mL phytic acid-betaine (the molar ratio of 3:1) aqueous solution exhibited the highest penetration rate and cumulative release amount (54.5 mg/cm 2 ). Then the influence of phytic acid-betaine (3:1) on the tested transdermal materials were evaluated by multiple characterizations including porosity, scanning electron microscopy (SEM), thermogravimetry (TG), and Fourier transform infrared spectra (FT-IR), etc., and no obvious damage was observed on the skin surface. Furthermore, no composition change of phytic acid-betaine was obviously found before and after transdermal process. Besides reported moisture retention (hygroscopicity), phytic acid-betaine variants showed strong antioxidant activity, calcium complexation ability and little irritation to human skin. Especially, related bioactive oil-in-DES microemulsion was prepared to broaden their application forms for the first time. Furthermore, the intrinsic rules between viscosity and hydrogen bond were explored by quantum chemistry calculations to clarify the difference in their permeation behaviors, and the interactions between DES components and tyrosinase were evaluated by molecular docking. As the result, above DESs played the dual roles of active ingredients and self-promoting penetration agents.