甘草酸-F127/TPGS混合纳米胶束的制备及其大鼠在体肠吸收研究

Preparation of glycyrrhizic acid-F127/TPGS mixed nanomicelles and its in vivo intestinal absorption in rats

目的制备甘草酸(GL)-普朗尼克F127(F127)/聚乙二醇1000维生素E琥珀酸酯(TPGS)混合纳米胶束(MMs)(GL-F127/TPGS-MMs),以改善GL的口服吸收。方法采用薄膜分散法制备GL-F127/TPGS-MMs,以胶束包封率、载药量为评价指标,单因素实验优化处方及工艺,包括F127与TPGS的比例、聚合物的质量浓度、GL的用量、水化温度、水化时间;采用透射电镜考察胶束形态;以吸收速率常数(Ka)和表观吸收系数(Papp)为评价指标,采用大鼠在体单向肠灌流法考察GL-F127/TPGS-MMs的肠吸收特性。结果优化得到处方和工艺为TPGS 180 mg、F127270 mg、GL 70 mg、水化温度50℃、水化时间3 h。所制备GL-F127/TPGS-MMs澄明度好,平均粒径为(28.20±5.63)nm,多分散系数为0.20±0.06,Zeta电位为(?5.24±1.55)mV,包封率为(97.57±5.29)%,载药量为(13.13±0.71)%;胶束呈球形,可见明显的囊泡结构。与回肠段比较,GL在空肠段吸收较好,且差异有统计学意义(P<0.05);与GL原料药比较,GL-F127/TPGS-MMs的肠吸收较好,且差异有统计学意义(P<0.05)。结论所制备的GL-F127/TPGS-MMs显著地提高了GL的体内吸收。

Objective To prepare glycyrrhizic acid(GL)-Pluronic F127(F127)/polyethylene glycol 1000 vitamin E succinate(TPGS)mixed nanomicelles(MMs)and improve oral absorption of GL.Methods GL-F127/TPGS-MMs was prepared by thin film dispersion method.The encapsulation efficiency and drug loading of MMs were used as evaluation indexes.The formulation and process,including the ratio of F127 to TPGS,the concentration of polymer and GL,hydration temperature and time,were optimized by the single factor experiment.The morphology of MMs was investigated by transmission electron microscopy.The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of GL-F127/TPGS-MMs with absorption rate constant(Ka)and apparent absorption coefficient(Papp)as evaluation indexes.Results The optimal formulation and process of GL-F127/TPGS-MMs were as follows:TPGS 180 mg,F127270 mg,GL 70 mg,hydration temperature 50℃and hydration time 3 h.The prepared GL-F127/TPGS-MMs had good clarity and the particle size,polydispersity index,and Zeta potential were(28.20±5.63)nm,0.20±0.06,and(?5.24±1.55)mV,respectively.The encapsulation efficiency and drug loading were(97.57±5.29)%and(13.13±0.71)%,respectively.The MMs were spherical with distinct vesicle structure.The absorption of GL in the jejunum segment was significantly higher than that in the ileum segment(P<0.05).Compared with raw GL,GL-F127/TPGS-MMs had a statistically significant higher absorption rate in the intestinal segment(P<0.05).Conclusion The prepared GL-F127/TPGS-MMs could significantly improve the absorption of GL in vivo.