目的 制备染料木素（genistein，GEN）-维生素E琥珀酸酯（VES）-聚乙二醇1000维生素E琥珀酸酯（TPGS）纳米胶束，以改善染料木素口服生物利用度。方法 薄膜分散法制备GEN-VES-TPGS纳米胶束，以胶束平均粒径、包封率、载药量为评价指标，单因素实验优化处方及工艺，包括TPGS、VES、GEN的用量、水化体积、水化温度、水化时间；对优选处方工艺的胶束形态、体外释放度及大鼠体内药动学进行了考察。结果 优化得到处方为TPGS 200 mg、VES 30 mg、GEN 6 mg，水化体积15 mL、水化温度50℃、水化时间3 h。所制备GEN-VES-TPGS纳米胶束澄明度好，平均粒径为（43.50±1.65）nm，包封率为（98.99±0.69）%，载药量为（2.57±0.04）%；胶束呈球形，可见明显的囊泡结构，GEN原料药和纳米胶束在体外均呈现缓释特征；大鼠ig给药药动学结果显示，所构建的GEN纳米胶束生物利用度为GEN原料药的162.96%。结论 所制备的GEN-VES-TPGS纳米胶束粒径小，稳定性好，显著地提高了GEN口服生物利用度。

Objective To prepare GEN-VES-TPGS nano-micelles and improve the oral bioavailability of genistein (GEN). Methods GEN-VES-TPGS nano-micelles, made by film hydration, were evaluated with particle size, entrapment efficiency, and drug-loading as indexes. Single factor experiment was used to optimize the formulation and productive technology, including dosages of TPGS, VES, GEN, hydration volume, temperature, and time. Morphology of nano-micelles, release rate in vitro, and pharmacokinetics in rat were investigated. Results The results showed GEN-VES-TPGS nano-micelles presented with good clarity, appropriate particle diameter (43.50 ±1.65) nm, negative charge, when the dosages of TPGS, VES, GEN were 200, 30, and 6 mg, respectively. Meanwhile, a condition of 15 mL, 50℃ at 3 h to hydrate was necessary to prepare. In this setting, the encapsulation efficiency of the nano-micelles was (98.99 ±0.69)% and drug-loading rate was (2.57 ±0.04)%. The pharmacokinetic results in rats showed the oral bioavailability of GEN-VES-TPGS nano-micelles was 162.96% of the GEN APIs. Conclusion The prepared GEN-VES-TPGS nano-micelles have small particle size and good stability, and increase the oral bioavailability of GEN evidently.

国家自然科学基金资助项目（81403117）