雷公藤甲素经皮给药制剂的研究与筛选  

Screening of transdermal drug delivery preparations of triptolide

作　　者：管咏梅 雷方方 王舒慧 朱卫丰 陈丽华 吴璇 陈颖翀 GUAN Yong-mei;LEI Fang-fang;WANG Shu-hui;ZHU Wei-feng;CHEN Li-hua;WU Xuan;CHEN Ying-chong(Key Laboratory of Modern Chinese Medicine Preparations,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中草药》2023年第10期3093-3100,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82060722);江西省自然科学基金资助项目(20202BAB206081);2021年度江西省研究生创新专项资金资助项目(YC2021-S504)。

摘　　要：目的为降低雷公藤甲素经皮给药刺激性、提高经皮渗透性,筛选雷公藤甲素经皮给药载体,为雷公藤甲素经皮给药新型给药系统的开发奠定基础。方法制备雷公藤甲素立方液晶、醇质体、胶束、凝胶等制剂,采用动态透析释药法考察雷公藤甲素不同剂型的体外释药特性;采用改良的Franz扩散池法考察雷公藤甲素不同剂型体外经皮渗透性能;通过皮肤刺激性实验评价雷公藤甲素不同剂型皮肤刺激性减毒效果。结果雷公藤甲素立方液晶、醇质体、胶束、凝胶8 h累积释放度分别为(51.40±1.19)%、(100.67±1.37)%、(89.25±4.27)%、(42.61±4.27)%,24 h累积渗透量分别为(0.46±0.02)、(0.48±0.04)、(0.44±0.03)、(0.27±0.02)mg/cm^(2)。皮肤刺激性结果表明,雷公藤甲素立方液晶、醇质体、胶束均呈轻度刺激性,而凝胶为中等刺激性。结论雷公藤甲素不同剂型有着不同特性,相较醇质体、胶束、凝胶而言,雷公藤甲素立方液晶有良好的缓控释作用和经皮渗透效果,同时能显著降低雷公藤甲素的皮肤刺激性,是雷公藤甲素经皮给药最佳剂型。Objective In order to reduce the irritation and improve the transdermal permeability of triptolide,the transdermal drug delivery carrier of triptolide(TP)was screened to lay a foundation for the development of a new transdermal drug delivery system of triptolide.Methods Triptolide lipid cubic liquid crystalline nanoparticles,ethosomes,micelles,gel and other preparations were prepared.The in vitro release characteristics of different formulations of triptolide were investigated by dynamic dialysis release method.The improved Franz diffusion cell method was used to investigate the in vitro percutaneous permeability of different formulations of triptolide.The skin irritation attenuation effect of different dosage forms of triptolide was evaluated by skin irritation test.Results The cumulative release rates of triptolide lipid cubic liquid crystalline nanoparticles,ethosomes,micelles and gel at 8 h were(51.40±1.19)%,(100.67±1.37)%,(89.25±4.27)%and(42.61±4.27)%,respectively.The cumulative permeation amounts at 24 h were(0.46±0.02),(0.48±0.04),(0.44±0.03)and(0.27±0.02)mg/cm^(2),respectively.The results of skin irritation showed that triptolide lipid cubic liquid crystalline nanoparticles,ethosomes and micelles had mild irritation,while triptolide gel had moderate irritation.Conclusion Different dosage forms of triptolide have different characteristics.Compared with ethosomes,micelles and gels,triptolide cubic liquid crystalline nanoparticles has good sustained and controlled release effect and percutaneous penetration effect,and can significantly reduce the skin irritation of triptolide.It is the best dosage form for transdermal administration of triptolide.

关 键 词：雷公藤甲素 立方液晶 醇质体 胶束 凝胶 体外释放 经皮渗透性 皮肤刺激性 

分 类 号：R283.6[医药卫生—中药学]