羟基喜树碱磁性脂质体的制备及其靶向性特征试验

目的:优选羟基喜树碱(HCPT)磁性脂质体的制备工艺并验证其体内靶向聚集性.方法:以经油酸表面改性的Fe3O4磁性纳米粒作为材料,大豆卵磷脂、胆固醇为原料,利用薄膜分散-超声法制备羟基喜树碱磁性脂质体,以包封率为评价指标,采用正交试验法对羟基喜树碱脂质体的制备工艺进行优选.引入微透析技术,动态、连续地考察磁性脂质体的肿瘤局部聚集性.结果:羟基喜树碱磁性脂质体的最佳制备工艺为药脂比25:1,磷脂-胆固醇80:30,制备温度45 ℃,水化介质pH6.8的磷酸盐缓冲液(PBS).在此条件下,最高包封率66.8％,载药量2.57％.在荷瘤小鼠体内磁靶向定位试验中,HCPT磁性脂质体外加磁场组的肿瘤部位药物浓度较不加磁场组和注射液组高,表明HCPT磁性脂质体在外加磁场引导下具有明显的磁靶向性效果.结论:使用油酸改性的Fe3O4联合应用薄膜分散-超声法制备的HCPT磁性脂质体粒径均一,稳定分散,包封率较高,磁靶向性好.

Preparation and Target Characteristic Test of Hydroxycamptothecin Magnetic Liposomes

Objective:To optimize preparation technology of hydroxycamptothecin(HCPT) magnetic liposomes and examine its in vivo targeting aggregation.Method: With Fe3O4 magnetic nanoparticles as material whose surface was modified by oleic acid,soybean lecithin and cholesterol as raw material,HCPT magnetic liposomes was prepared by film dispersion-ultrasound method with encapsulation efficiency as index,preparation technology of HCPT magnetic liposomes was optimized by orthogonal test.Local tumor aggregation of magnetic liposomes was dynamic and continuous investigated by microdialysis technique.Result: Optimized prearation conditions of HCPT magnetic liposomes were as follows:ratio of drug-lipid 25∶1,phospholipid-cholesterol 80∶30,preparation temperature 45 ℃,hydration medium phosphate buffer solution(pH 6.8).The highest encapsulation efficiency of 66.8%,drug loading of 2.57%.In tumor-bearing mice in vivo magnetic targeting positioning test,the drug concentration at site of tumor of HCPT magnetic liposomes additional magnetic field group was higher than group without magnetic field and injection group,it proved that HCPT magnetic liposomes had obvious magnetic targeting effect under guidance of additional magnetic field.Conclusion: HCPT magnetic liposomes showed particle size uniformity,stable dispersion,high encapsulation efficiency and good magnetic targeting,which prepared by oleic acid-modified Fe3O4 and film dispersion-ultrasonic method.