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 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.
Zhongguo Zhong Yao Za Zhi. 2021 Oct;46(20):5278-5283. doi: 10.19540/j.cnki.cjcmm.20210330.303.
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 material 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 550 μm. 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.
雷公藤甲素（TP）是雷公藤的主要活性和毒性成分，存在生物利用度低、吸收差、血浆浓度低和致死剂量小等局限性。微针（MN）是皮下注射针和透皮贴剂的结合体，是一种物理促渗系统。溶解微针（DMNs）可以根据降解速率的特定需求进行定制。在本研究中，采用两步离心法制备了载雷公藤甲素的溶解微针（DMNs-TP）。以成型性和机械强度为指标，研究了制备DMNs时聚乙烯醇（PVA）与聚乙烯吡咯烷酮K30（PVP K30）的最佳比例、基质溶液含水量、脱模方法和增塑剂。采用高效液相色谱法测定载药量，并在光学显微镜下观察形态特征。通过苏木精-伊红（H&E）染色研究其力学性能，并用Franz扩散池检测其体外皮肤渗透特性。通过实验，我们确定最佳背衬材料应为PVA和PVP K30（3∶1），基质材料与水的最佳比例应为3∶4。制备的DMNs-TP呈金字塔形，表面光滑，长度约为550μm。每片贴剂（2.75 cm²）的载药量为（153.41±2.29）μg，且TP位于针的上部。体外皮肤渗透试验结果表明，DMNs-TP中TP在24 h内的累积渗透量达到80%，而很少有TP溶液渗透过皮肤，这证明DMNs促进了TP的透皮递送。
