雷公藤甲素自溶性微针的制备及体外经皮渗透性研究  

Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration

作　　者：陈鑫 张永萍 徐剑 宋信莉 刘耀 郭玲 汪祖华 CHEN Xin;ZHANG Yong-ping;XU Jian;SONG Xin-li;LIU Yao;GUO Ling;WANG Zu-hua(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Guizhou Engineering Research Center for Traditional Chinese Medicine and Ethnic Medicine Processing and Preparation,Guiyang 550025,China;National Engineering Research Center of Miao′s Medicines,Guiyang 550025,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州省中药民族药炮制与制剂工程技术研究中心,贵州贵阳550025 [3]国家苗药工程技术研究中心,贵州贵阳550025

出　　处：《中国中药杂志》2021年第20期5278-5283,共6页China Journal of Chinese Materia Medica

基　　金：贵州省高层次创新型人才“百层次”人才项目(黔科合平台人才[2015]4030);贵州省国内一流学科建设项目(GNYL[2017]008);贵州省药物新剂型心工艺科技创新人才团队项目(黔科合平台人才[2017]5655);贵州省教育厅研究生创新计划项目(3411-4110000520605);贵州省科技厅2017年度学术新苗培养及创新探索专项(黔科合平台人才[2017]5735号-26);贵州省教育厅普通高等学校科技拔尖人才支持计划项目(黔教合KY字[2017]074)。

摘　　要：雷公藤甲素(triptolide,TP)是中药雷公藤属植物的主要活性和毒性成分,具备生物利用度低以及吸收差、血药浓度难以达到治疗浓度、致死量小等特点。微针(microneedles,MNs)作为一种集注射与透皮为一体的物理促渗技术,其中的自溶性微针(dissolving microneedles,DMNs)还可根据治疗需求制作不同降解速度的自溶性微针。该文将雷公藤甲素与自溶性微针结合,采用两步离心法制备DMNs-TP,并以成型性和机械性能作为考察指标,考察制备DMNs的基质比例、基质液的含水量、脱模方法及塑形剂的种类等。用HPLC测定其载药量,光学显微镜表征,并用H&E染色考察其机械性能,采用Franz扩散池考察其体外透皮性能。通过实验确定DMNs-TP背衬层的最佳处方为PVP-PVA,两者比例为3∶1,基质与水比例为3∶4,DMNs-TP针体呈四棱锥形,表面平整,长度约为550μm,每片面积为2.75 cm^(2),含药量为(153.41±2.29)μg,药物位于针体上部。离体皮肤渗透结果显示,24 h后DMNs-TP中TP的累积渗透量可达80%,而TP溶液则透过很少。实验证明微针对TP透皮递送具有良好的促进作用,能有效穿透大鼠离体皮肤。Triptolide(TP),the main active and toxic component of Tripterygium wilfordii,has the limitations of low bioavailability,poor absorption,low concentration in plasma,and small lethal dose.Microneedle(MN),the hybrid of hypodermic needle and transdermal patch,is a physical penetration-enhancing system.Dissolving microneedles(DMNs)can be tailored to specific needs of degradation rate.In this study,the TP-loaded DMNs(DMNs-TP)were prepared with the two-step centrifugation method.The optimal ratio of PVA to PVP K30,water content in matrix solution,demoulding method,and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength.The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope.The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics.Through the experiment,we confirmed that the optimal backing ma-terial should be PVA and PVP K30(3∶1)and the optimal ratio of matrix material to water should be 3∶4.The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550μm.Each patch(2.75 cm^(2))had the drug loading capacity of(153.41±2.29)μg,and TP was located in the upper part of the needle.The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80%in 24 h,while little TP solution penetrated the skin,which proved that DMNs promoted the transdermal delivery of TP.

关 键 词：雷公藤甲素 自溶性微针 经皮给药系统 两步离心法 体外透皮性能 

分 类 号：R283.6[医药卫生—中药学]