Chen Jiasheng, Chen Zhenzhen, Wang Wentao, Wang Liyang, Zheng Jiaqi, Wu Shiqiong, Pan Yuru, Li Sai, Zhao Jie, Cai Zheng
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China.
AAPS PharmSciTech. 2024 Jul 13;25(6):163. doi: 10.1208/s12249-024-02881-z.
Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.
一些糖苷类药物可通过肠道葡萄糖转运体（IGTs）进行转运。口服药物制剂中使用的表面活性剂会影响转运蛋白的功能。本研究旨在探讨常用表面活性剂泊洛沙姆188和吐温80对IGTs药物转运能力的影响。先前的研究表明天麻素是IGTs的最佳药物底物。以天麻素作为探针药物，通过药代动力学和原位单通道肠灌注来评估这两种表面活性剂对SD大鼠肠道吸收的影响。然后，采用RT-PCR和蛋白质免疫印迹法检测这两种表面活性剂对葡萄糖转运体和紧密连接蛋白表达的影响。此外，通过苏木精-伊红染色评估表面活性剂对肠道通透性的影响。结果发现，泊洛沙姆188（0.5%、2.0%和8.0%）和吐温80（0.1%和2.0%）的所有实验与空白组相比均无显著差异。然而，当使用0.5%吐温80时，天麻素的AUC增加了约32%。IGTs表达的变化与天麻素的肠道吸收相关。在0.5%吐温80时观察到IGTs表达显著增加。总之，在推荐使用范围内，泊洛沙姆188对IGTs的药物转运能力影响极小。然而，0.5%吐温80可使IGTs表达增加，从而显著增强IGTs的药物转运能力。不过，0.1%和2.0%吐温80无显著影响。
