注射用多西他赛脂质体的制备及其体内外评价  

Preparation and in vivo-in vitro evaluation of docetaxel liposome for injection

作　　者：王栋海 杨光丽 邹伟伟 严守升 宫新江 周英兰 杨清敏 王晶翼 

机构地区：[1]山东省注射用微粒给药新技术重点实验室,济南250100 [2]齐鲁制药有限公司药物研究院,济南250100

出　　处：《中国新药杂志》2011年第1期24-28,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2010ZX09401-302-4-2);山东省泰山学者建设工程专项经费资助

摘　　要：目的:制备多西他赛脂质体,对其体内外性质进行评价。方法:采用改良薄膜分散法结合冷冻干燥工艺制备多西他赛脂质体冻干粉;用激光粒度仪考察了脂质体的粒径分布和Zeta电位;超滤法测定了包封率;以市售多西他赛注射液为对照,比较体外释放、大鼠骨髓抑制和裸鼠体内肿瘤抑制情况。结果:多西他赛脂质体平均粒径为92 nm,Zeta电位为-52.3 mV,包封率>95%,24 h累积释放率为84.1%;相同剂量下,多西他赛脂质体比多西他赛注射液的骨髓抑制作用降低,但二者对HT-29移植瘤的抑制作用相同。结论:本实验所制备的多西他赛脂质体包封率较高、稳定性较好;与多西他赛注射液相比,毒性较低,同时具有相同的抗肿瘤效力。Objective：To prepare docetaxel liposomes and characterize its in vitro and in vivo properties.Methods： Docetaxel liposomes were prepared by modified film dispersion-high pressure homogenization and lyophilization.Vesicle size and Zeta potential were determined by the Zetasizer Nano ZS.Encapsulation efficiency was evaluated by ultrafiltration method.The in vitro release,bone marrow toxicity and tumor inhibition of liposomal docetaxel were investigated in comparation with docetaxel injection.Results： The mean particle size,Zeta potential and encapsulation efficiency of the lyophilized liposomes were 92 nm,-52.3 mV,and 95%,respectively.Docetaxel was released by 84.1% from liposomes in vitro within 24 h.The toxicity of bone marrow inhibition of docetaxel liposome was lower than that of docetaxel injection.However,the anti-tumor effect of the liposomal docetaxel was as good as the docetaxel injection.Conclusion： The docetaxel liposomes have a high encapusulation efficiency and long time shelf-life.The bone marrow toxicity of liposomal docetaxel in rats is lower than that of docetaxel injections,while the anti-tumor effect is the same.

关 键 词：多西他赛 脂质体 包封率 体外释放 骨髓抑制 

分 类 号：R971.1[医药卫生—药品]