R_8多肽修饰表阿霉素与双氢青蒿素脂质体处方优选及含量测定

Formulation and Content Determination of Epirubicin-Dihydroartemisinin Liposomes Modified with R_8 Polypeptide

目的:优选R_8多肽修饰表阿霉素与双氢青蒿素脂质体的处方,并建立脂质体中表阿霉素的含量测定方法。方法:以薄膜分散法-硫酸铵梯度法制备R_8多肽修饰表阿霉素与双氢青蒿素脂质体,采用星点设计-响应面法对卵磷脂/胆固醇(EPC/Chol)质量比、超声功率、卵磷脂/表阿霉素(EPC/EPI)质量比进行优选,采用高效液相色谱法(HPLC)法测定脂质体中表阿霉素的含量。结果:优选后卵磷脂/胆固醇(EPC/Chol)质量比为4∶1,超声功率为300 W,卵磷脂/表阿霉素(EPC/EPI)质量比为25∶1,所得脂质体平均包封率为(94.5%±0.51%)(n=3);脂质体中表阿霉素的平均含量为(150.01±1.26)μg/mL(n=3)。结论:优化所得处方稳定,适用于制备R_8多肽修饰表阿霉素与双氢青蒿素脂质体;建立的HPLC法准确可靠,简单快速,可用于测定脂质体中表阿霉素的含量。

Objectives:To optimize the formulation of R8 polypeptide modified epirubicin plus dihydroartemisinin liposomes and to establish a method for determination of epirubin in liposomes. Methods:Thin-film diffusion and ammonium sulfate gradient method were used to prepare R8 polypeptide modified epirubicin plus dihydroartemisinin liposomes. The central composite design-response surface method was used to optimize the quality ratio of lecithin/cholesterol(EPC/Chol),ultrasonic power and the quality ratio of lecithin/epirubicin(EPC/EPI),and HPLC method was adopted to determine the content of epirubicin.Results:After the optimal formulation,the mass quality ratio of lecithin/cholesterol(EPC/Chol)was 4 ∶1,the ultrasonic power was 300 W,and the mass quality ratio of lecithin/epirubicin(EPC/EPI)was 25∶1. The average encapsulation rate of liposomes was(94.50%±0.51%)(n=3),the average content of epirubicin in liposomes was(150.01±1.26)μg/mL(n=3). Conclution:The optimized formulation stable and suitable for the preparation of R8 polypeptide modified epirubicin plus dihydroartemisinin liposomes.The established HPLC method is accurate,reliable,simple and rapid,and can be used to determine the content of epirubicin in liposomes.