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壳聚糖包覆左旋多巴脂质体冻干制剂的制备及大鼠口服药动学

Preparation of freeze-dried chitosan-liposome containing L-dopa and pharmacokinetics in rats after oral administration

  • 摘要: 目的 : 制备壳聚糖包覆的左旋多巴脂质体以增加左旋多巴生物利用度,减少血药浓度波动;研究冻干的最佳处方及工艺。 方法 : 逆相蒸发法制备左旋多巴脂质体并以壳聚糖包覆,采用冷冻干燥法制备脂质体冻干制剂,单因素实验考察不同因素对冻干后包封率的影响;高效液相色谱法研究大鼠口服壳聚糖包覆的左旋多巴脂质体的药动学。 结果 : 最佳冻干处方为:磷脂浓度50 mg/mL,药脂比1∶10,壳聚糖浓度0.17%,冻干保护剂蔗糖用量2%。其包封率为(34.34±0.65)%(n=6)。与溶液组相比,大鼠口服壳聚糖包覆的左旋多巴脂质体后血药浓度达峰时间后延,且长时间维持在较高水平,生物利用度提高到溶液组的400%以上。 结论 : 选用合适冻干工艺可以得到包封率大于30%的左旋多巴脂质体冻干制剂。壳聚糖包覆脂质体能够提高左旋多巴生物利用度,减少血药浓度波动。

     

    Abstract: Aim :To prepare chitosan-coated L-dopa liposomes,and to optimize the formulation and freeze-drying processing parameters of L-dopa liposomes. Methods :The liposomes were prepared by using reverse phase evaporation followed by freeze-drying,and effects of the factors on the entrapment efficiency of L-dopa liposome were studied.Pharmacokinetics of L-dopa in rats receiving oral dosing of L-dopa solution and chitosan-coated liposomes were investigated after HPLC determination of L-dopa levels in rats plasma. Results :The optimized freeze-drying formulation composed of 50 mg/mL of phosphatidyl choline (PC),0.17% chitosan,2% sucrose as freeze-drying protectant,and a ratio of 1∶10 of drug loading to lipid.Entrapment efficiency(EE) was calculated to be (34.34±0.65)%(n=6).Compared with L-dopa solution,c max was delayed and higher levels maintained for a longer period after oral administration of L-dopa liposomes in rats.Moreover,the magnitude of the increased L-dopa dioavailability in rats was more than 400% of that of L-dopa solution. Conclusion :Freeze-dried liposomal preparation with EE of more than 30% was obtained by the proposed approch.Chitosan coated L-dopa liposomes increased the L-dopa bioavailability in rats.

     

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