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CPEs with high log P, molecular weight and polarizability showed highest ERpermeation, which indicated that its enhancement action site was skin according to its βR/P value less then 1, due to it interacted with skin lipid strongly and obtained the lowest diffusion rate in skin. Thus, it increased the disruption level of highly ordered arrangement of intercellular lipid bilayers, which was characterized by ATR-FTIR, Raman, confocal laser scanning microscopy and molecular dynamics simulation. In conclusion, physicochemical properties of