白蛋白阿霉素磁纳米粒在大鼠体内的生物分布

目的：观察白蛋白阿霉素磁纳米粒肝动脉给药与肝动脉给予高剂量的游离药物在体内生物分布上的差异。通过直接测量组织中阿霉素的浓度，进一步证实白蛋白阿霉素磁纳米粒的靶向性。方法：大鼠正中开腹，胃十二指肠动脉插管。实验组：肝动脉注射白蛋白阿霉素磁纳米粒（相当0．5mg/kg阿霉素）左肝外叶应用磁场30min，磁场去除后，动物处死。对照组：肝动脉注射10倍于实验组剂量的阿霉素（5mg/kg),30min后处死。动物处死后，取靶区肝组织、非靶区肝组织、心、肾、脾和肺捣碎、匀浆，用乙醇提取法提取阿霉素，用荧光光度计测量。结果：实验组左肝外叶应用磁场30min，磁区肝组织阿霉素的浓度较非磁区肝组织的阿霉素浓度明显升高，磁共肝组织阿霉素浓度为非磁区肝组织的2．6倍，对照组靶区肝组织和非靶区肝组织的阿霉素浓度无统计学差异，对照组和心和肾组织的阿霉素浓度平均为实验组的9倍以上，脾为4．6倍，肺两组之间无统计学差异。而对照组靶区肝组织的阿霉素只有磁区肝组织阿霉素浓度的1／4。实验组心、肾、肺和脾组织与靶区肝组织阿霉素浓度的比值大大低于对照组。结论：通过纳米粒加磁场的方法从肝动脉给予阿霉素在靶区产生的药物浓度比肝动脉给予10倍剂量的游离阿霉素在靶区产生的药物浓度高3倍。而在心、肾和脾的阿霉素浓度比对照组大为降低。另外，实验组心、肾、肺和脾组织和与靶区肝组织阿霉素的比值比对照组明显降低，其意义若在靶区产生同样的阿霉素的浓度，实验组肝外脏器的阿霉素浓度将大大降低对照组。

THE BIODISTRBUTION OF MAGNETICALBUMIN NANOPARTICLES CONTAINING ADRIAMYCIN

Objective: Theaim of this study to determine whether differences existed in administration of adriamycin between magntetic albumin microspheres and free drug. The magnetic target of magnetic nanoparticles was further identified by measurementof tissne concentration of adriamycin. Methods:Abdominal exposure was carried out through a midleine abdominal incision,A cannulawas inserted into gastroduenal artery. In the experimental Magnetic albumin nanoparticles containing adriamycin was injected intohepatic artery (equivalent dose of free Adriamycin 0.5mg/kg). After magnetic field was removed,the animal was irmmediately sacrificed. Administration of 10 times dose of free adriamycin served as a control. The target liver tissue. nontarget liver tissue, heart, kidney,lung and spleen were weighed and homogenized in a 5％ Hcl solution in ethanol at 4℃ for 2min. The homogenates were centrifuged and the supernates were examined for total fluorescence using a spectrophotofiuoromenter. Results: In the experimental group,the concentration of adriarnycin of target site of liver was 2.6 times as high as that of nontarget site of liver. The concentration of adriamycin in control group was increased over 9 times,compared to experimental group. Spleen was 4.6 times. No statistics difference inlung was found between two groups. Even though the dose of adriamycin of control group was 10 times as high as that of experimentalgroup,the concentration of adriamycin of target site of liver in control group was only one- forth of that in experimental group. Theratio of concentration of heart,kidney,lung and spleen to target liver tissue tissue in experimental group decreased grestly, compared tocontrol group. Conclusions:Even if diose of free drug was 10 times high as that of nanoparticles, the concentration of adriamycin produced by free drug was only one-forth of that by magnetic nanoparticles in target site of liver. However, the greatly, compared to experimental group. In addition, the ratio of heart, kidney, lung and spleen tissue to target site of liver in expermental group decreasedgreatly, retative to control group, which means the concentration of adriamycin of heart,kidney, lung and spleen tissue i experimentalgroup would be much less than that in control group if equal concentration of adriamycin was produced in target site.