阿霉素白蛋白磁纳米粒在正常肝脏的靶向性

目的：观察阿霉素白蛋白磁纳米粒在正常肝脏中的磁靶向性。并观察阿霉素白蛋白磁纳米粒在全身各脏器的分布特征。方法：大鼠正中开腹，胃十二指肠动脉插管固定。实验组，左肝外叶加磁场，肝动脉注射阿霉素白蛋白的磁纳米粒（相当于阿霉素0．5mg/kg)，磁场应用30min移去磁场后，动物立即处死，对照组：左肝外叶外不加磁场，肝动脉注射同等剂量的纳米粒后30min处死。动物处死后，立即取靶区肝、非靶区肝、心、肾、脾、肺、小肠和胃作γ计数。肝组织作组织学切片。结果：左肝外叶应用磁场30min后，磁共肝组织的放射活性较非磁共肝组织的放射活性明显增加（P＜0．0001），磁区肝组织与非磁区肝组织的放射活性比值为2．6。而对照组磁区肝组织与非磁区肝组织的放射活性之间无统计学差异。肝外脏器的放射活性明显降低。除实验组肺的放射活性较对照组明显下降外，其它脏器两组之间没有统计学差异，另外，实验组，心、肾、脾、肺和小肠与靶区肝组织和的放射活性比值较对照组明显降低，胃与靶区肝组织的放射活性比值两组之间无统计学差异。注入纳米粒的70％－80％分布于肝脏，其它脏器含量极少。病理切片显示磁共小动脉中见大量纳米粒存在，对照组及非磁共肝中纳米粒很少见。结论：阿霉素白蛋白磁纳米粒在正常肝脏组织中有明显的磁靶向性，阿霉素白蛋白磁纳米粒主要分布于肝脏，其它脏器含量较少。实验组心、肾、脾、肺和小肠与靶区组织的放射活性比值明显降低，说明磁的存在使这些脏器的相对药物暴露明显减少。

THE TARGET DISTRIBUTION OF MAGNETIC ALBUMINNANOPARTICLES CONTAINING ADRIAMYCIN IN NORMAL RAT LIVER

Objective:The aim of this study is to verify the effect of magnetic field application on magnetic nanoparticles, distributed throughout the in vivo, normal rat liver, and observer resulting characteristic in the rat organs. Methods: Abdoninal exposurewas carride out through a midline abdominal incision. A cannula was inserted into the gastroduodenal artery. In the experimentalgroup,the left lateral lobe of the liver was exposed to the magnetic field for 30 minutes. Magnetic albumin nanoparticles containingadriamycin were injected into the hepatic artery (equivalent dosage of 0.5mg/kg of free Adriamycin). After the magnet was removed,the animal was immediately sacrificed. Administration of an equal dose of nanoparticles in the absence of a magnetic field served as acontrol. The target liver tissue, non- target liver tissue. heart, kidneys, lungs, spleens, stomach and small intestines were analyzed forI125 - counts. The histology of the liver tissue was examined. Results: In the experiment group, the radioactivity of the target sites was2.6 times higher than the non- target sites in the liver. In the control group,no statistical differences were found between that of the target sites and non-target sites. In both experimental and control group, the radioactivity of the heart,kidneys, lungs, spleen, stomach and small intestines was much lower than that of the liver (including target and non- targets sites). The radioactivity of the lungsin the experiment group decreased significantly, relative to the control group. In addition, 70～80％ of the injected radioactive nanoparticles collected in liver. The histology examination indicated that a large amount of nanoparticles accumulated in,and in somecases filled, the arterioles in the experimental group. In the control group,aggregation of nanoparticles was not found;there only nonaggreated, single nanoparticles dispersed in the hepatic sinus. Conclusions: In the presence of a magnetic field, magnetic albuminnanoparticles accumulated at a target site. The radioactivity of the target sites was 2.6 times higher than that of the non- target sites.70～80％ of the injected radioactivity dose collected in the liver. In the experiment group, the ratio of radioactivity at the heart, kidneys, spleen, lungs and intestines to the radioactivity at the liver target sites decressed significantly in comparison to the control group.This means that the overall percentage of harmful organ exposure to drugs in the experimental group was effectively reduced.