雷公藤甲素阿魏酸醇质体凝胶的制备与经皮渗透性研究

Preparation and transdermal permeation of triptolide and ferulic acid ethosomes gel in vitro

采用改良后的Franz扩散池法，以小鼠腹部皮肤为模型进行体外透皮扩散，收集不同时间点的接收液，用HPLC测定其中阿魏酸的浓度、用LC-MS／MS测定雷公藤甲素的浓度，比较醇质体凝胶、普通凝胶、乳膏3种剂型的透皮速度、透皮量与皮肤储量的差别，以探索雷公藤甲素阿魏酸醇质体凝胶中阿魏酸、雷公藤甲素的体外透皮特性并与普通凝胶组和乳膏组比较。结果，雷公藤甲素阿魏酸醇质体凝胶、普通凝胶和乳膏中阿魏酸稳态透皮速率分别为5．2685，8．9909，12．0420ug·cm^-2·h^-1，皮肤滞留量分别（30．2348±1．5254），（20．4026±0．4026），（7．6353±1．0942）μg·cm^-2；雷公藤甲素阿魏酸醇质体凝胶中雷公藤甲素的稳态透皮速率为67．2380ng·cm^-2·h^-1约为乳膏的1．24倍，普通凝胶的3．28倍，皮肤滞留量为（371．3514±35．3171）ng·cm^-2约为乳膏的3．35倍，普通凝胶的5．25倍。故雷公藤甲素阿魏酸醇质体凝胶透皮效果良好，有助于临床安全给药。

The aim of this study was to prepare triptolide and ferulic acid ethosomes gel, investigate its transdermat permeation, and compare the results with ordinary gel and cream. Improved Franz diffusion cell method was used in the transdermal delivery experiment with rat abdominal skin as in vitro model. The receptor fluid at different time points was collected; ferulic acid concentration was deter- mined by high performance liquid chromatography （HPLC） and triptolide concentration was determined by liquid chromatography-elec- trospray ionization mass spectrometry （LC-MS/MS）. Then the penetration rate, transdermal volume and skin reserve of three dosage forms （ hydroplasy gel, ordinary gel, and cream） to investigate the transdermal properties of ferulic acid and triptolide in vitro of triptol- ide and ferulic acid ethosomes gel. The results showed that the steady penetration rate of ferulic acid was 5. 268 5, 8. 990 9, 12.042 0 μg·cm^-2·h^-1 respectively in triptolide and ferulic acid ethosomes gel, ordinary gel and cream; the skin retention was （30. 234 8 ± 1. 525 4）, （20.402 6 ± 0.402 6）, （7. 635 3 ± 1. 094 2） μg·cm-2. The steady-state permeation rate of triptolide was 67. 238 0, 67. 238 0 ng·cm^-2·h^-1 in triptolide and fendic acid ethosomes gel, about 1.24 times of cream and 3.28 times of ordinary gel; the skin retention was （371. 351 4±35. 317 1 ） ng·cm^-2, about 3.35 times of cream and 5.25 times of ordinary gel. Therefore, the etho- somes gel showed good transdermal absorption property and it may be good for clinical safety administration.