NGR-单壁碳纳米管-紫杉醇复合物的制备及其靶向性研究

张艳艳付旭东,刘康栋,赵继敏,董子明,张振中

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (20) : 1748-1754.

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中国药学杂志 ›› 2013, Vol. 48 ›› Issue (20) : 1748-1754. DOI: 10.11669/cpj.2013.20.015
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NGR-单壁碳纳米管-紫杉醇复合物的制备及其靶向性研究

  • 张艳艳1,a,付旭东2,刘康栋1,a,赵继敏1,a,董子明1,*,张振中1,b,*
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Preparation and Tumor Targeting of NGR-SWCNTs-Paclitaxel

  • ZHANG Yan-yan
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摘要

目的 探讨NGR-单壁碳纳米管-紫杉醇复合物的最佳制备方法及其靶向性。方法 溶液共混法制备单壁碳纳米管-紫杉醇,将其连接NGR构建NGR-单壁碳纳米管-紫杉醇载药系统,并对其进行表征。考察单壁碳纳米管-紫杉醇制备中表面活性剂的种类、探头超声次数、碳纳米管的量等因素对载药量和包封率的影响。以S180荷瘤小鼠为模型,分别静注NGR-单壁碳纳米管-紫杉醇,单壁碳纳米管-紫杉醇和紫杉醇,采用高效液相色谱法测定小鼠脾、心、肝、肺、肾、肿瘤各组织的药物浓度,用靶向效率(TE)评价制剂的靶向性。结果 碳纳米管-紫杉醇为1∶2;表面活性剂Poloxamer188和苯丙氨酸以7∶3混合;选择功率600 W,超声15次为探头超声条件制得单壁碳纳米管-紫杉醇,与NGR反应得到NGR-单壁碳纳米管-紫杉醇复合物,其包封率为(83.9±2.7)%,载药量为(69.3±1.5)%,Zeta电位为(-22.6±1.5)mV,平均粒径为(182.1±2.4)nm。在小鼠脾、肝、肺和肿瘤组织中NGR-单壁碳纳米管-紫杉醇和单壁碳纳米管-紫杉醇的AUC显著大于紫杉醇组(P<0.05,P<0.01)。在小鼠脾、肝、肺组织中单壁碳纳米管-紫杉醇和NGR-单壁碳纳米管-紫杉醇的靶向效率无明显差别,在心、肾组织中的靶向效率有所下降(P<0.05),在肿瘤中靶向效率分别为6.78%和21.33%,差异显著(P<0.01)。结论 优化条件制备的NGR-单壁碳纳米管-紫杉醇复合物制备工艺和储存稳定性好,载药量和包封率高,且能显著提高紫杉醇的肿瘤靶向性。

Abstract

To investigate the best method for preparing NGR-SWCNTs-paclitaxel and observe its targeting efficency. METHODS SWCNTs-paclitaxel was prepared by solution mixing, and then conjugated with NGR to obtain a novel paclitaxel delivery system:NGR-SWCNTs-paclitaxel. Taking loading efficiency and encapsulate efficiency as index,studied the influential factors of the preparation of NGR-SWCNTs-paclitaxel by surfactant、times and frequency of probe sonography, quantity of carbon nano tube. The drug concentration in different tissue were detected by high performance liquid chromatography(HPLC).The targeting efficiency were used to evaluate the tissue targeting of NGR-SWCNTs-paclitaxel, SWCNTs-paclitaxel and paclitaxel.RESULTS SWCNTs-paclitaxel was prepared by SWCNTs-paclitaxel was 1∶2; Poloxamer188-phenylalanine was 7∶3;probe sonography 600 W,15 times. SWCNTs-paclitaxel conjugated with NGR formed NGR-SWCNTs-paclitaxel . Its loading efficiency was (83.9±2.7)% and encapsulate efficiency was (69.3±1.5)%. The Zeta potential was(-22.6±1.5)mV, partical size was about(182.1±2.4)nm. The AUC of NGR-SWCNTs-paclitaxel and SWCNTs-paclitaxel in mice slpeen、liver、lung and tumor were increased obviously compared with paclitaxel(P<0.05,P<0.01).The targeting efficiency of SWCNTs-paclitaxel and NGR-SWCNTs-paclitaxel in heart and kidney were decreased(P<0.05), and in tumor the targeting efficiency was 6.78% and 21.33% separately, the difference was significantly(P<0.01). CONCLUSION The preparation of NGR-SWCNTs- paclitaxel was practicable by solution mixing. The loading efficiency and encapsulate efficiency of NGR-SWCNTs-paclitaxel are higher. NGR-SWCNTs-paclitaxel can enhance tumor targeting of paclitaxel obviously.

关键词

NGR / 单壁碳纳米管 / 紫杉醇 / 溶液共混 / 肿瘤靶向

Key words

NGR / SWCNTs / paclitaxel / solution mixing / tumor targeting

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导出引用
张艳艳付旭东,刘康栋,赵继敏,董子明,张振中. NGR-单壁碳纳米管-紫杉醇复合物的制备及其靶向性研究[J]. 中国药学杂志, 2013, 48(20): 1748-1754 https://doi.org/10.11669/cpj.2013.20.015
ZHANG Yan-yan,FU Xu-dong,LIU Kang-dong,ZHAO Ji-min,DONG Zi-ming,ZHANG Zhen-zhong . Preparation and Tumor Targeting of NGR-SWCNTs-Paclitaxel[J]. Chinese Pharmaceutical Journal, 2013, 48(20): 1748-1754 https://doi.org/10.11669/cpj.2013.20.015
中图分类号: R944   

参考文献

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基金

中央高校基本科研业务费专项资金资助(JKP2011005);国家基础科学人才培养基金(J0630858);天然药物活性组分与功效国家重点实验室(中国药科大学)资助项目(SKLNMKF201204)

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