Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

Abstract Objective To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim. ( Z. bungeanum oil) on active components in externally-applied traditional Chinese medicines. Methods Five model drugs, geniposide, puerarin, ferulic acid, tetramethylpyrazine, and osthole, were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin. Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z. bungeanum oil. The molecular interactions between the oil and the polar head groups in stratum corneum (SC) lipids were monitored using molecular dynamic simulation, and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action. Results As oil concentration increased, the log ER flow trended toward a negative linear relationship with the lipophilicity of drugs. After treatment with Z. bungeanum oil, a mild lifting up and wrinkle on the SC surface were observed, and appeared to become more pronounced as oil concentration increased. There was no significant difference between the control and the Z. bungeanum oil at different concentrations in terms of saturation solubility of GP, while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased. The oxygen-containing constituents in Z. bungeanum oil, such as terpinen-4-ol and 1,8-cineole, which accounted for 57.95% of total oil, could form stable hydrogen bonds with the polar head group of ceramide 3. Conclusion Z. bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity, including the extremely hydrophilic and lipophilic drugs, whereas it exhibited greater enhancement activity for strongly hydrophilic drugs. The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient, saturation solubility, and the interactions with SC lipids.