R_8GD多肽修饰大黄素脂质体的处方优选及含量测定

Formulation Optimization and Content Determination of R_8GD Polypeptide Modified Emodin Liposomes

目的采用星点设计-效应面法优选R_8GD多肽修饰大黄素脂质体的最佳处方,并建立R_8GD多肽修饰大黄素脂质体中大黄素的含量测定方法。方法采用薄膜-超声分散法制备R_8GD多肽修饰大黄素脂质体。以包封率为指标,采用星点设计-响应面法优化处方中胆固醇和大黄素的用量及超声波细胞捣碎机的功率。通过方法学考察,建立高效液相色谱法(HPLC)测定R_8GD多肽修饰大黄素脂质体中大黄素含量的方法。结果 R_8GD多肽修饰大黄素脂质体的最优处方为磷脂22 mg、胆固醇4.5 mg、大黄素1.2 mg,超声波细胞捣碎机的功率为500 W,其包封率为95.78%±0.64%(n=3)。含量测定中,R_8GD多肽修饰空白脂质体对主药含量的测定无干扰。R_8GD多肽修饰大黄素脂质体中大黄素在5～35μg/ml范围内线性关系良好;脂质体中大黄素平均加样回收率大于95%;脂质体中大黄素的含量为229.872±1.53μg/ml。结论星点设计-响应面法优选出了大黄素脂质体的最佳处方。HPLC准确、简便、重现性好,可用于大黄素脂质体中药物含量的质量控制。

Objective To optimize the formulation of R8GD polypeptide modified emodin liposomes using central composite design-response surface methodology and to establish a method for content determination of R8GD polypeptide modified emodin liposomes. Methods R8GD polypeptide modified emodin liposomes were prepared by thin film-ultrasonic diffusion method. With the encapsulation efficiency as the index, the central composite designresponse surface methodology was used to optimize the amount of cholesterol and emodin in the prescription, and the power of the ultrasonic cell crusher. A methodological investigation was conducted to determine the content of emodin in R8GD polypeptide modified liposomes by high performance liquid chromatography (HPLC). Results The optimal formulation of 5 ml R8GD polypeptide modified emodin liposomes was consist of 22 mg phospholipid, 4.5 mg cholesterol and 1.2 mg emodin and the power of the ultrasonic cell crusher was 500 W. The encapsulation efficiency of emodin in the liposomes was 95.78 %±0.64 %(n=3). In the content determination, R8GD polypeptide modified blank liposomes did not interfere the determination of the main drug content. The emodin has a good linear relationship in the range of 5-35 μg/ml in R8GD polypeptide modified emodin liposomes;the recovery rate was above 95 %;the content of emodin was 229.872±1.53 μg/ml. Conclusion The central composite design-response surface methodology could optimize the best prescription of R8GD polypeptide modified emodin liposomes. The established HPLC method is accurate, simple, reproducible, and can be used for the quality control of drug content in R8GD polypeptide modified emodin liposomes.