羟基喜树碱肝靶向脂质体的制备与表征

背景:羟基喜树碱难溶于水,目前临床使用的制剂多为内酯开环形成的羧酸盐,静脉给药后广泛分布于体内各种组织器官,不良作用明显. 目的:制备一种肝靶向的羟基喜树碱脂质体,改善其水溶性差及肿瘤局部药物浓度低等不足. 方法:采用薄膜分散-高压均质法制备肝靶向羟基喜树碱脂质体,扫描电镜观察脂质体的表面形态,激光粒径仪测定粒径大小、分布及Zeta电位,高效液相色谱检测纳米粒的包封率及体外释放周期. 结果与结论:制备的脂质体呈类球形,平均粒径205.6 nm,多元分散系数0.39,平均Zeta电位为-38.6 mV,包封率为78.1%,载药率为1.28%,在体外48 h累积释放83.5%.提示薄膜分散-高压均质法可制备粒径均匀、包封率高、释放平稳的肝靶向羟基喜树碱脂质体.

Preparation and characterization of hepatocyte-targeting liposome containing hydroxycamptothecin

BACKGROUND:Because of poor water solubility of hydroxycamptothecin,carboxylic acid salt that is formed by opening lactone ring is mostly used in clinic.Hydroxycamptothecin widely distributes in all kinds of the tissues and the organs in vivo following intravenous injection,which will result in serious toxicity and side effects.OBJECTIVE:To prepare a hepatocyte-targeting liposome containing hydroxycamptothecin to improve its water solubility and local drug concentration in tumor.METHODS:The hepatocyte-targeting liposome containing hydroxycamptothecin was prepared by thin film dispersion-high pressure homogeneous method.Its morphology was examined by scanning electron microscope.The particle size,distribution and zeta potential were measured by laser scattering instrument.The encapsulation efficiency and in vitro release period were measured by high-performance liquid chromatography.RESULTS AND CONCLUSION:The prepared liposome was spherical with a mean size of 205.6 nm,dispersion coefficient of 0.39,and zeta potential of-38.6 mV.The encapsulation efficiency was 78.1%,and the in vitro cumulative release rate was 83.5% within 48 hours.The above results indicate that thin film dispersion-high pressure homogeneous method can prepare an ideal hepatocyte-targeting liposome containing hydroxycamptothecin,which has even particle,high encapsulation efficiency and stable release.