基于甜茶苷的漆黄素载药纳米胶束的制备及其抗结肠炎活性

Preparation of Fisetin Nanomicelles Based on Rubusoside and Its Anti-colitis Activity

制备基于两亲性甜茶苷的漆黄素载药纳米胶束(Fis/Rub胶束),以提高漆黄素的药代动力学特性和疾病治疗效果。采用薄膜分散法制备Fis/Rub胶束,并对其理化性质进行测定;采用亚铁还原能力实验检测Fis/Rub胶束的抗氧化活性;透析法和高效液相色谱法检测Fis/Rub胶束的体外释放能力;考察Fis/Rub胶束的药代动力学特性和体内抗结肠炎活性。所得Fis/Rub胶束的粒径为(7.6±1.2)nm,电位为(-3.86±0.43)mV。甜茶苷纳米胶束可有效包封漆黄素;提高漆黄素在水中的溶解度((19.12±0.84)mg·mL^(-1));改善漆黄素的体外释放;增强漆黄素的抗氧化活性。大鼠体内药物动力学结果显示,与漆黄素混悬液相比,Fis/Rub胶束可提高漆黄素的口服生物利用度达5.5倍。药效学研究表明,口服Fis/Rub胶束可有效改善硫酸葡聚糖盐(DSS)诱导的小鼠溃疡性结肠炎的治疗效果。Fis/Rub这一新型制剂改善了漆黄素水溶性差等不足,具有潜在的进一步开发研究和临床意义。

To prepare the fisetin nanomicelles on amphiphilic rubusoside(Fis/Rub),to enhance the pharmacokinetics and therapeutic effect of Fis.Fis/Rub nanomicelles were prepared by film dispersion method and to determine their physicochemical properties;The antioxidant activity of Fis/Rub nanomicelles was determined by ferrous reducing capacity experiment;The in vitro release capacity of Fis/Rub micelles was determined by dialysis method and HPLC;To investigate the pharmacokinetic properties and in vivo anti-colitis activity of Fis/Rub micelles.The particle size of Fis/Rub micelles was(7.6±1.2)nm,and the potential was(-3.86±0.43)mV.The water solubility of Fis in Fis/Rub was(19.12±0.84)mg·mL^(-1).in vitro release characterization of Fis in Fis/Rub was greatly improved.The antioxidant activity of Fis was also provoked improved.The pharmacokinetic results in rats showed that Fis/Rub micelles increased the oral bioavailability of laccaxanthin by 5.5 times compared with laccaxanthin suspension.The pharmacokinetic results in rats showed that Fis/Rub micelles increased the oral bioavailability of Fis up to 5.5 times compared with Fis suspension agent.Pharmacodynamic studies have shown that oral administration of Fis/Rub micelles can effectively improve the therapeutic effect of ulcerative colitis in mice model in-duced by dextran sodium sulfate(DSS).Fis/Rub has improved the poor water solubility of Fis,which has potential further development and clinical significance.