Investigation of the Enhancement Effect of Evodia rutaecarpa Volatile Oil on Transdermal Delivery of Total Glucosides of Paeony: Mechanistic Insight Based on Interactions Among Drug, Enhancer, and Skin

Background: Total glycosides of peony (TGP) have therapeutic potential for immune-related and inflammatory skin diseases, but their skin absorption is not satisfactory. This study aims to investigate howEvodia rutaecarpavolatile oil (VO-ER) enhances the permeability of TGP.Methods: Safety assessment was conducted through cell delivery and skin erythema tests. The chemical composition of VO-ER was identified via GC-MS. The study was conducted using modified Franz diffusion cells, microdialysis, confocal laser scanning microscopy (CLSM), attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), molecular docking and molecular dynamics simulations (MD), laser Doppler flowmetry (LDF), and the western blotting method.Results: The study found that VO-ER promotes the permeation of total glycosides of peony in a concentration-dependent manner by disrupting the intercellular lipid tissue structure, downregulating the expression of claudin-1, claudin-7, and occludin, and improving local microcirculation, thereby promoting the absorption of TGP.Conclusions: VO-ER enhances the transdermal absorption of TGP through multiple mechanisms, such as disrupting the skin lipid barrier, downregulating tight junction proteins, and improving local skin microcirculation. This study provides a theoretical basis for VO-ER as a safe and effective new transdermal penetration enhancer, offering support for the development of topical preparations containingEvodia rutaecarpaandPaeonia lactiflora.