中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (2): 260-267.doi: 10.3969/j.issn.2095-4344.2017.02.018

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

复合叶酸-碳纳米管-紫杉醇的司盘-聚乙二醇超声对比剂微泡的制备

刘俊希1，张  杰1，2，张  宇1，赵  越1，万国靖3，李国忠2
  

  1. 1佳木斯大学黑龙江药学研究所，黑龙江省佳木斯市  154007；2哈尔滨医科大学附属第一医院神经内科，黑龙江省哈尔滨市  150081；3武警黑龙江总队医院药剂科，黑龙江省哈尔滨市  150070
  • 收稿日期:2016-12-09 出版日期:2017-01-18 发布日期:2017-02-27
  • 通讯作者: 张杰，博士，讲师，佳木斯大学黑龙江药学研究所，黑龙江省佳木斯市 154007；哈尔滨医科大学附属第一医院神经内科，黑龙江省哈尔滨市 150081 张宇，硕士，教授，佳木斯大学黑龙江药学研究所，黑龙江省佳木斯市 154007
  • 作者简介:刘俊希，1990年生，黑龙江省肇源县人，汉族，佳木斯大学在读硕士，主要从事天然药物化学研究。
  • 基金资助:

    国家自然科学基金青年基金(81601616)；黑龙江省博士后基金(LBH-Z15164)；黑龙江省科学基金(H2016086)；佳木斯大学研究生科技创新项目(LM2015_091)；佳木斯大学科技创新团队基金(CXTD-2013-05)

Preparation of span-poly(ethylene glycol) ultrasound contrast agent microbubbles combined with folate-carbon nano tube-paclitaxel

Liu Jun-xi1, Zhang Jie1, 2, Zhang Yu1, Zhao Yue1, Wan Guo-jing3, Li Guo-zhong2
    

  1. 1Pharmaceutical Research Institute of Heilongjiang Province, Jiamusi University, Jiamusi 154007, Heilongjiang Province, China; 2Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China; 3Department of Pharmacy, Heilongjiang General Hospital of Arm Police Force, Harbin 150070, Heilongjiang Province, China
  • Received:2016-12-09 Online:2017-01-18 Published:2017-02-27
  • Contact: Zhang Jie, M.D., Lecturer, Pharmaceutical Research Institute of Heilongjiang Province, Jiamusi University, Jiamusi 154007, Heilongjiang Province, China; Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China Zhang Yu, Master, Professor, Pharmaceutical Research Institute of Heilongjiang Province, Jiamusi University, Jiamusi 154007, Heilongjiang Province, China
  • About author:Liu Jun-xi, Studying for master’s degree, Pharmaceutical Research Institute of Heilongjiang Province, Jiamusi University, Jiamusi 154007, Heilongjiang Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81601616; the Post Doctoral Foundation of Heilongjiang Province, No. LBH-Z15164; the Natural Science Foundation of Heilongjiang Province, No. H2016086; the Scientific and Technologic Innovation Program for the Graduates of Jiamusi University, No. LM2015-091; the Scientific Innovation Group of Jiamusi University, No. CXTD-2013-05

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被引次数

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摘要：

文章快速阅读：

 

文题释义：
功能化碳纳米管：采用浓酸回流法对碳纳米管进行羧基化；制备叶酸壳聚糖偶合物；通过壳聚糖将叶酸连接到羧基化的碳纳米管上，作为靶向因子；再将紫杉醇负载到叶酸修饰后的靶向碳纳米管上，制得靶向载药的碳纳米管复合物，实现碳纳米管的功能化。
复合超声对比剂微泡：采用声振空化的方法，制备以司盘和聚乙二醇为膜材、包覆功能化碳纳米管和氮气的复合微泡，经过洗涤和离心，得到粒径均一、性质稳定、空心结构的微泡。通过正交试验优化制备工艺条件，最终制得具有增强超声显影潜力的复合功能化碳纳米管的超声对比剂微泡。

背景：传统超声对比剂功能单一，灵敏度、清晰度和准确度受客观影响因素较大，无法同时实现诊断与治疗的作用。碳纳米管呈特殊的网状中空管腔结构，具有增强显影的潜力，通过非共价吸附、共价键合及内部包埋等方法得到功能化碳纳米管，生物相容性好，药物负载率高。基于此，将载药的碳纳米管加入到超声对比剂微泡结构中，制备一种新型的复合碳纳米管运载体系的多功能超声对比剂微泡。
目的：制备复合叶酸-碳纳米管-紫杉醇(folate-carbon nano-tube-paclitaxel，FA-CNTs-PTX)的司盘-聚乙二醇(Span-PEG)超声对比剂微泡，研究微泡的形貌、粒径、以及微泡中碳纳米管和紫杉醇的负载率。
方法：先采用声振空化法制备Span-PEG微泡，并通过正交实验优化制备工艺，再通过静电自组装、π-π吸附等原理合成FA-CNTs-PTX中间体。然后，将FA-CNTs-PTX中间体复合在Span-PEG微泡中，得到复合FA-CNTs-PTX的Span-PEG超声对比剂微泡。采用扫描电镜和透射电镜观察微泡的形貌，采用激光粒度分析仪测定微泡的粒径分布及平均粒径，采用紫外分光光度法测定微泡中碳纳米管和紫杉醇的负载率。
结果与结论：制备的复合FA-CNTs-PTX的Span-PEG微泡表面光滑、平均粒径为442 nm，微泡中碳纳米管和紫杉醇的负载率分别为1.69%和47.9%。成功将FA-CNTs-PTX靶向载药复合物包覆于Span-PEG微泡中，微泡为空心球体，粒径分布均匀且为纳米级别，该复合微泡有望成为一种集造影和靶向治疗为一体的超声对比剂。

关键词: 生物材料, 纳米材料, 超声对比剂, 诊断, 治疗, 靶向, 碳纳米管, 静电自组装, 紫杉醇, 叶酸, 国家自然科学基金

Abstract:

BACKGROUND: As the sensitivity, clarity and accuracy of traditional ultrasound contrast agents are easy to be affected by objective factors, it is difficult to achieve diagnose and therapy simultaneously. Carbon nano tubes (CNTs) possess a specific reticular, hollow and tubular structure and the potential to enhance the ultrasound imaging. The functional CNTs obtained through non-covalent adsorption, covalent bonding and internal embedding hold a good biocompatibility and high drug loading efficiency. So the drug loaded CNTs are added into the microbubble to synthesize a multi-functional ultrasound contrast agent.
OBJECTIVE: To prepare the span-poly(ethylene glycol) (span-PEG) ultrasound contrast agent microbubble combined with folate-CNTs-paclitaxel (FA-CNTs-PTX) and to investigate its appearance, particle size as well as loading efficiency of CNTs and PTX.
METHODS: Firstly, the span-PEG microbubble was prepared using the acoustic cavitation method and its preparation process was optimized through the orthogonal experiment. Then the FA-CNTs-PTX compound was synthesized by the electrostatic self-assembly and π-π adsorption principle. In the end, the span-PEG ultrasound contrast agent microbubble combined with FA-CNTs-PTX was obtained by loading the FA-CNTs-PTX into the span-PEG microbubble. The appearance of the composite microbubble were observed using scanning and transmission electron microscopes, the distribution and average particle size were detected by laser particle size analyzer, and the loading efficiency of CNTs and PTX was measured through ultraviolet spectroscopy.
RESULTS AND CONCLUSION: The composite microbubble had a smooth surface and the average particle size was 442 nm. The loading efficiency of CNTs and PTX in the composite microbubble was 1.69% and 47.9%, respectively. To conclude, the FA-CNTs-PTX targeting drug delivery system is successfully loaded into the span-PEG microbubble. The composite microbubble is a hollow sphere that has uniform nanoscaled particle size distributions, which is expected to become an ideal ultrasound contrast agent involved in angiography and targeting therapy.  

Key words: Ultrasonics, Nanotubes, Carbon, Tissue Engineering

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