Synergistic Effect and Mechanism of Cineole and Terpineol on In-vitro Transdermal Delivery of Huperzine A from Microemulsions

The aim of the present study was to investigate the influence and the mechanisms of cineoleand terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, andtheir potential synergistic effect on the permeation enhancement. The transdermal deliveryof huperzine A from microemulsions with different concentrations of cineole and terpineolthrough the rat abdominal skin was determined by Franz-type diffusion cells. The partitioncoefficient of huperzine A between the full thickness skin and microemulsion was determined.Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was carriedout to analyze the effects of cineole and terpineol on the biophysical properties of the stratumcorneum (SC) and the mechanisms of permeation enhancement. These results indicated thatcineole and terpineol could synergistically increase the transdermal delivery of huperzine Afrom microemulsions through increasing the partition and diffusion coefficients of huperzineA. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancingmechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains,disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole andterpineol, acting synergistically to enhance the transdermal delivery of huperzine A frommicroemulsions, might provide an alternative permeation enhancer combination for thetransdermal delivery of huperzine A.