载药磁纳米微粒在荷瘤小鼠体内的靶向性实验研究
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摘要
目的 :应用高效液相色谱法考察在外磁场协同下载阿霉素金磁复合微粒于荷瘤小鼠体内靶向分布特性。方法 :建立小鼠肝细胞癌动物模型,并分成空白对照组、单纯磁阿霉素组和磁阿霉素加磁场组。空白对照组经尾缘静脉注射生理盐水,单纯磁阿霉素组和磁阿霉素加磁场组分别注射同等剂量的载阿霉素金磁复合微粒溶液,注射后于磁阿霉素加磁场组肿瘤靶区体表施加磁场固定(5 000 Gs、1 h)。然后移去磁场并立即处死各组小鼠,分别采集血液并完整摘取心、肝、肾和肿瘤组织标本。应用高效液相色谱法测定各组小鼠血液及各组织中阿霉素浓度,评价其在小鼠体内的靶向性。结果:经外置磁场固定作用后,靶区肿瘤组织中阿霉素浓度明显高于其他非靶区组织,而其他非靶区组织中(除心脏外)阿霉素浓度与空白对照组相当。在没有外置磁场作用时,阿霉素则在体内各组织中呈弥散性分布,但肝脏和肿瘤组织中阿霉素浓度较高。结论:磁纳米微粒作为药物载体具有明显的磁控靶向性,能将药物有效富聚于靶区肿瘤组织中。磁靶向药物有望成为最有效的抗肿瘤药物新剂型而用于临床。
Objective To investigate the targeting distribution of adriamycin-bearing gold magnetic particle in the tumorbearing mice by using high-performance liquid chromatography and external magnetic field. Methods Mouse hepatocellular carcinoma models were established and then divided into a control group(group A), a group with adriamycin-bearing magnetic nano-particles(group B) and a group with external field and adriamycin-bearing magnetic nano-particles(group C). The mice in group A were administrated with physiological saline in the tail veins, and the ones in group B and C were infused with the solution of adriamycin-bearing gold magnetic particles. Some external magnetic field(5 000 Gs, 1 h)was posed on the target areas of the mice in group C and then removed after a while. All the mice in the three groups were killed, and the blood and the specimens of the hearts, livers, kidneys and tumor tissues were collected. The concentrations of adriamycin in the blood and tissues were detected with high-performance liquid chromatography to evaluate in vivo targeted distribution in mice. Results External field made the adriamycin concentrations in the targeted tumor areas significantly higher than those in non-targeted areas, and the non-targeted areas except the heart had the concentrations equivalent to those in the control group. When the external field was absent, adriamycin had diffused distribution in the tissues while high concentrations in the liver and tumor tissues. Conclusion Magnetic nano-particle shows magnetically controlled targeting when used as drug-bearing carrier and can concentrate the drug in the targeted tumor tissues. Magnetically targeted drug may be popularized clinically as a new-type antineoplastic agent.
Objective To investigate the targeting distribution of adriamycin-bearing gold magnetic particle in the tumorbearing mice by using high-performance liquid chromatography and external magnetic field. Methods Mouse hepatocellular carcinoma models were established and then divided into a control group(group A), a group with adriamycin-bearing magnetic nano-particles(group B) and a group with external field and adriamycin-bearing magnetic nano-particles(group C). The mice in group A were administrated with physiological saline in the tail veins, and the ones in group B and C were infused with the solution of adriamycin-bearing gold magnetic particles. Some external magnetic field(5 000 Gs, 1 h)was posed on the target areas of the mice in group C and then removed after a while. All the mice in the three groups were killed, and the blood and the specimens of the hearts, livers, kidneys and tumor tissues were collected. The concentrations of adriamycin in the blood and tissues were detected with high-performance liquid chromatography to evaluate in vivo targeted distribution in mice. Results External field made the adriamycin concentrations in the targeted tumor areas significantly higher than those in non-targeted areas, and the non-targeted areas except the heart had the concentrations equivalent to those in the control group. When the external field was absent, adriamycin had diffused distribution in the tissues while high concentrations in the liver and tumor tissues. Conclusion Magnetic nano-particle shows magnetically controlled targeting when used as drug-bearing carrier and can concentrate the drug in the targeted tumor tissues. Magnetically targeted drug may be popularized clinically as a new-type antineoplastic agent.
引文
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[7]赵志娟,丁红,罗斌华.肺靶向多柔比星微球小鼠体内组织分布特性研究[J].中国药学杂志,2012,47(5):354-357.
[8]何强芳,李国明,朱洁民.磁性氟尿嘧啶壳聚糖微球的制备及其释药性能[J].应用化学,2006,23(2):209-211.
[9]李艳,赵玲,路西明,等.磁性微粒靶向给药系统治疗消化道恶性肿瘤的基础研究与临床初探[J].中国现代应用药学杂志,2006,23(9):925-928.
[10]龚连生,张德阳,刘恕.磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性[J].中华肝胆外科杂志,2003,9(9):543-546.
[11]Ensminger W D,Gyves J W.Regional cancer chemotherapy[J].Cancer Treat Rep,1984,68:101-105.
[12]叶鹏,宋金春,李娟.氟尿嘧啶脂质体在小鼠体内的组织分布及靶向性评价研究[J].中国药房,2011,22(13):1 168-1 170.
[2]成党校,唐敏章.阿霉素磁微球的制备及在家兔肺内的靶向定位[J].第四军医大学学报,1996,17(1):39-41.
[3]赵玉莹,谢忠艳,薛凡.磁性药物微球治疗恶性肿瘤的进展[J].黑龙江医学,2010,34(10):745-748.
[4]王艳萍,徐维平,苏育德,等.纳米磁性材料在肿瘤治疗中的应用研究进展[J].亚太传统医药,2012,8(3):183-184.
[5]Hofman M A,Purba J S,Swaab D F.Annual variations in the vasopressin neuron population of the human suprachiasmatic nucleus[J].Neuroscience,1999,53(4):1 103-1 112.
[6]凌丽,张武雄,朱亮.抗肿瘤靶向微粒给药系统的研究进展[J].广东药学院学报,2010,26(1):107-110.
[7]赵志娟,丁红,罗斌华.肺靶向多柔比星微球小鼠体内组织分布特性研究[J].中国药学杂志,2012,47(5):354-357.
[8]何强芳,李国明,朱洁民.磁性氟尿嘧啶壳聚糖微球的制备及其释药性能[J].应用化学,2006,23(2):209-211.
[9]李艳,赵玲,路西明,等.磁性微粒靶向给药系统治疗消化道恶性肿瘤的基础研究与临床初探[J].中国现代应用药学杂志,2006,23(9):925-928.
[10]龚连生,张德阳,刘恕.磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性[J].中华肝胆外科杂志,2003,9(9):543-546.
[11]Ensminger W D,Gyves J W.Regional cancer chemotherapy[J].Cancer Treat Rep,1984,68:101-105.
[12]叶鹏,宋金春,李娟.氟尿嘧啶脂质体在小鼠体内的组织分布及靶向性评价研究[J].中国药房,2011,22(13):1 168-1 170.