高级检索

    大黄酚混合胶束的制备及其体内药动学研究

    Preparation and in Vivo Pharmacokinetics of Chrysophanol Mixed Micelles

      摘要
    • 摘要:
      目的  制备大黄酚-普朗尼克F127/甘草酸混合胶束(Chry-F127/GA)，对其进行表征并考察其在大鼠体内的药动学。
      方法 采用溶剂蒸发法制备Chry-F127/GA，并运用单因素试验结合响应面法优化处方。按最优处方制备Chry-F127/GA后，对其进行表征。将大黄酚原料药和Chry-F127/GA胶束溶液经尾静脉注射给药，于不同时间点采血，采用HPLC测定大黄酚血药浓度。所得血药浓度数据用PK Solver 2.0程序进行拟合，得到药动学参数。
      结果 制备Chry-F127/GA的最优处方：大黄酚投药量为3 mg，药载比为1︰23，甘草酸的百分含量为60%，载体浓度为4 mg·mL−1。包封率、载药量、粒径、Zeta电位分别为(84.99±1.63)%、(3.54±0.07)%、(118.43±1.76)nm和(−22.03±1.47)mV。放置14 d内，胶束的粒径、多分散指数和包封率均未发生明显变化。通过透射电子显微镜观察到所制备的纳米胶束外观均一，呈球形。差示扫描量热法与傅里叶-红外光谱法测定结果表明，大黄酚以无定型形式存在于混合胶束中。细胞摄取试验结果表明，胶束剂型提高了HepG-2细胞对Chry的摄取量。药动学结果显示，相较于大黄酚原料药组，Chry-F127/GA胶束组的AUC0-t升高，全身清除率(total body clearance，CL)降低，平均滞留时间(mean residence time，MRT)延长。
      结论 制备得到的Chry-F127/GA胶束包封率高，在体内停留时间长，发挥作用时间延长，能够提高大黄酚的生物利用度。

       

      Abstract:
      OBJECTIVE To prepare chrysophanol-Pluronic F127/glycyrrhizic acid(Chry-F127/GA) mixed micelles, characterize them, and evaluate their in vivo pharmacokinetics in rats.
      METHODS Chry-F127/GA was prepared using the solvent evaporation method. The formulation was optimized using single-factor tests combined with response surface methodology. The optimized Chry-F127/GA was characterized. Chrysophanol bulk drug and Chry-F127/GA micelle solution were administered via tail vein injection. Blood samples were collected at different time points, and the plasma concentration of chrysophanol was determined by HPLC. The obtained plasma concentration data were fitted using the PK Solver 2.0 program to derive pharmacokinetic parameters.
      RESULTS The optimal formulation for preparing Chry-F127/GA was as follows: chrysophanol amount of 3 mg, drug loading ratio of 1∶23, glycyrrhizic acid percentage content of 60%, and carrier concentration of 4 mg·mL−1. The encapsulation rate, drug loading, particle size, and Zeta potential were (84.99±1.63)%, (3.54±0.07)%, (118.425±1.76)nm, and (−22.03±1.47)mV, respectively. No significant changes in micelle particle size, polydispersity index(PDI) and encapsulation rate were observed over 14 d of storage. Transmission electron microscopy(TEM) revealed that the prepared nanomicelles had a uniform, spherical appearance. Differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR) results showed that chrysophanol existed in an amorphous form within the mixed micelles. Cellular uptake assay results demonstrated the micellar formulation enhanced the uptake of chrysophanol by HepG-2 cells. Pharmacokinetic results showed that compared to the chrysophanol bulk drug group, the Chry-F127/GA micelle group exhibited increased AUC0-t, decreased total body clearance(CL), and prolonged mean residence time(MRT).
      CONCLUSION The prepared Chry-F127/GA micelles have a high encapsulation rate. With a long residence time and prolonged action time in vivo, Chry-F127/GA can improve the bioavailability of chrysophanol.

       

      • HTML全文
      • 参考文献(30)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回