张诗雨, 孙敬蒙, 李冬冬, 张欣, 张佳慧, 张炜煜. 花旗松素-磷脂/胆盐/聚维酮-K30胶束的构建及对酒精性肝损伤的保护作用J. 药学学报, 2025, 60(2): 488-497. DOI: 10.16438/j.0513-4870.2024-0758
引用本文: 张诗雨, 孙敬蒙, 李冬冬, 张欣, 张佳慧, 张炜煜. 花旗松素-磷脂/胆盐/聚维酮-K30胶束的构建及对酒精性肝损伤的保护作用J. 药学学报, 2025, 60(2): 488-497. DOI: 10.16438/j.0513-4870.2024-0758
ZHANG Shi-yu, SUN Jing-meng, LI Dong-dong, ZHANG Xin, ZHANG Jia-hui, ZHANG Wei-yu. Construction of Tax-PC/SDC/PVP-K30 micelles and their protective effect on alcoholic liver injuryJ. Acta Pharmaceutica Sinica, 2025, 60(2): 488-497. DOI: 10.16438/j.0513-4870.2024-0758
Citation: ZHANG Shi-yu, SUN Jing-meng, LI Dong-dong, ZHANG Xin, ZHANG Jia-hui, ZHANG Wei-yu. Construction of Tax-PC/SDC/PVP-K30 micelles and their protective effect on alcoholic liver injuryJ. Acta Pharmaceutica Sinica, 2025, 60(2): 488-497. DOI: 10.16438/j.0513-4870.2024-0758

花旗松素-磷脂/胆盐/聚维酮-K30胶束的构建及对酒精性肝损伤的保护作用

Construction of Tax-PC/SDC/PVP-K30 micelles and their protective effect on alcoholic liver injury

  • 摘要: 花旗松素(taxifolin, Tax) 已被证实可作为药食同源的可食用物质, 具有保护酒精性肝损伤作用, 然而其亲水性和渗透性均较差, 阻碍了Tax的临床应用。本研究制备了花旗松素-磷脂/胆盐/聚维酮-K30 (taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells, Tax-MLs) 纳米胶束, 采用Box-Behnken试验得到最佳制备工艺, 以透射电镜、傅里叶红外光谱等对Tax-MLs进行表征; 测定临界胶束浓度、平衡溶解度及油水分配系数等理化参数, 并通过体外消化模拟试验探讨Tax-MLs的释放规律; 酒精性肝损伤模型探讨Tax-MLs的体内药效。结果显示, Tax-MLs的平均粒径、多分散性指数及zeta电位分别为36.90 ± 4.57 nm、0.194 ± 0.01及-32.6 ± 0.35 mV, 透射电镜观测到Tax-MLs呈现大小均一, 分布均匀的类球形, 差式扫描量热分析和傅里叶红外光谱等证明Tax-MLs的形成; 理化性质方面, Tax-MLs相较Tax在水中的溶解度提高了92.02倍, 其在水中的油水分配系数也从0.43增加到1.14, 证明Tax-MLs能够提高其溶解度及渗透性; 体内药效学结果显示, 与Tax组相比, Tax-MLs低、中、高剂量组肝脏指数及血清中谷草转氨酶和谷丙转氨酶水平显著降低(P < 0.05), 增强肝组织中超氧化物歧化酶、谷胱甘肽活性, 降低丙二醛水平的效果更明显。Tax-MLs有效提高了药物的溶解度和渗透性, 并增强了对酒精性肝损伤的保护作用。本研究体内动物实验得到了长春中医药大学动物伦理委员会的批准(批准号: 2023601)。

     

    Abstract: Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by in vitro digestion simulation. Alcoholic liver injury model to explore the in vivo efficacy of Tax-MLs. The results showed that the average particle size, polydispersity index (PDI) and zeta potential of Tax-MLs were 36.90 ± 4.57 nm, 0.194 ± 0.01 and -32.6 ± 0.35 mV, respectively, and the uniform size and distribution of Tax-MLs were observed by transmission electron microscopy. The formation of Tax-MLs was proved by differential scanning calorimetry and fourier transform infrared spectroscopy. In terms of physicochemical properties, the solubility of Tax-MLs in water increased by 92.02 times compared with Tax, and its oil-water partition coefficient in water increased from 0.43 to 1.14, which proved that Tax-MLs could improve its solubility and permeability. The in vivo pharmacodynamic results showed that compared with the Tax group, Tax-MLs low, medium and high dose groups showed a significant reduction in liver indices and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH), and lowered the levels of malondialdehyde (MDA) more significantly in the hepatic tissues. Tax-MLs effectively improved drug solubility and permeability, and enhanced the protective effect against alcoholic liver injury. Animal experiments were conducted with approval from the Animal Ethics Committee of Changchun University of Traditional Chinese Medicine (approval number: 2023601).

     

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