外加磁场对半乳糖化白蛋白磁性阿霉素纳米粒在大鼠体内分布影响的研究
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R965

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国家高技术研究发展计划(863计划)


Study on effect of magnetic field application to targeting distribution of Gal-HSA magnetic nanoparticles containing adriamycin
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    摘要:

    目的观察半乳糖化白蛋白磁性阿霉素纳米粒(ADR-GHMN)在正常肝脏中的靶向性,并观察ADR-GHMN在全身各脏器的分布特征及外加磁场对其分布的影响.方法大鼠正中开腹,肝动脉插管并固定,肝动脉注射125I-ADR-GHMN(相当于阿霉素0.5 mg/kg),左外叶加磁场,磁场应用30 min,移去磁场后,动物立即处死;对照组:肝动脉注射ADR-GHMN,左外叶不加磁场,30min后,移去磁场后,动物立即处死,立即取靶区肝、非靶区肝、肾、心、肺、小肠、脾及周围血作γ计数.肝组织作病理切片.结果注入的纳米粒75~85%分布于肝脏,其它脏器极少.病理切片显示磁区小动脉见大量纳米粒存在,对照组及非磁区肝中纳米粒很少见.结论ADR-GHMN在正常肝组织中有明显的磁靶向性;在磁场作用下,ADR-GHMN主要分布于肝脏,其它脏器含量很少;试验组肾、心、肺、小肠、脾及外周血于对照组的放射活性比较明显降低,表明磁性物质的存在使这些脏器的相对药物暴露明显减少.

    Abstract:

    Objective: The aim of this study was to observe the hepatic targeting of Gal-HSA magnetic nanoparticles containing adriamycin and its effect of magnetic field application to targeting distribution in vivo,and probe into distributed characterization in the normal rat organs. Methods: Abominal exposure was carried out through a midline abdominal incision. A cannula was inserted into the hepatic artery and fixed up it. Gal-HSA magnetic nanoparticles containing adriamycin were injected into hepatic artery (equivalent dose of free adriamycin 0.5 mg/kg), after the left lateral lobe of the liver was expose to the magnetic field for 30 minute. The rat was immediately killed. Administration of equal close of nanoparticles in the absence of magnetic field served as a control. The targeting liver tissue, non-targeting liver, kindey, heart, lung, small intestine, spleen and blood was analyzed for 125I-counts. Liver tissue was examined for histology. Results: In either experimental group or control group, the radioactivity of heart kidney, lung, spleen small intestine was much less than liver (included target site and non-targeting site). The radioactivity of lung in experimental group decreased significantly, relative to dose distributed in liver (P<0.01). In addition, 75~85% of injected radioactivity dose distributed in liver. The histology examination demonstrated a lot of nanoparticles accumulated in arteriola.in control group, no accumulation of nanoparticles was found, only some single nanoparticles dispersed in hepatic sinus.Conclusions: Gal-HSA magnetic nanoparticles containing adriamycin in normal rat liver had remarkable hepatic targeting and good magnetic targeting. Dose which Gal-HSA magnetic nanoparticles containing adriamycin injected mainly distributed in liver, the ratio of heart, kidney, spleen,small intestine and blood in experiment group descreased significantly compared to control. It means the relative exposure of these organs in experimental group reduced, compared to control.

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张阳德,吴泽建,龚连生,潘一峰,黄林,席浩,李玉坤,王荣兵,翟登高,李浩.外加磁场对半乳糖化白蛋白磁性阿霉素纳米粒在大鼠体内分布影响的研究[J].中国医学工程,2004,(4):8-9,16

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