肺靶向羟基喜树碱脂质体的制备及其在小鼠体内的组织分布研究

目的： 研究羟基喜树碱脂质体的制备方法并考察其肺靶向及在小鼠体内的分布。方法： 采用薄膜分散－冻融法制备，添加D-甘露糖和十八胺修饰可得到肺靶向羟基喜树碱脂质体；用HPLC法测定给药后小鼠体内不同组织中的药物浓度。结果： 制得的脂质体平均粒径大于2 μm，表面电荷为+21.5 mV，包封率大于65%，稳定性好，符合要求。羟基喜树碱脂质体和注射液经小鼠尾静脉给药后，脂质体主要被肺摄取，在肺部停留的时间较普通注射剂显著延长，其相对摄取率r_e为60.72，脂质体组的肺靶向效率t_e为17.57。结论： 本实验制得羟基喜树碱脂质体具有较高包封率及稳定性，在小鼠肺部浓度高、滞留时间长，能达到肺靶向目的。

Preparation of lung targeting hydroxycamptothecin liposomes and its tissue distribution in mice

OBJECTIVE To prepare hydroxycamptothecin liposomes and observe its lung targets and distribution in mice.METHODS Hydroxycamptothecin liposomes were prepared by thin film method with freeze-thawing steps,and modified by lipid membrane with D-mannose and stearylamine.HPLC method was established and validated for determination of hydroxycamptothecin in tissues of mice.RESULTS Prepared hydroxycamptothecin liposomes demonstrated good stability and encapsulation efficiency was more than 65%.Average size was larger than 2 μm and Zeta potential of modified hydroxycamptothecin liposomes was+21.5 mV.Hydroxycamptothecin liposomes and hydroxycamptothecin injection were injected intravenously at a dose of 5 mg·kg^-1 to mice.Compared with injection,liposomes were characterized by slower clearance.HCPT concentration of lung targeting hydroxycamptothecin liposomes was much higher than that of HCPT injection in lung,r_e=60.72,t_e=17.57.CONCLUSION Preparation method of hydroxycamptothecin liposomes can significantly increase drug concentration in lung,and lung targeting efficiency was favorable.