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化学进展 2018, Vol. 30 Issue (1): 5-13 DOI: 10.7536/PC170922 前一篇   后一篇

• 综述 •

高分子多孔微球产品的制备及其在类病毒颗粒分离纯化中的应用

那向明1,2, 周炜清1, 李娟1, 苏志国1, 马光辉1*   

  1. 1. 中国科学院过程工程研究所生化工程国家重点实验室 北京 100190;
    2. 中国科学院大学 北京 100049
  • 收稿日期:2017-09-19 修回日期:2017-11-26 出版日期:2018-01-15 发布日期:2017-12-13
  • 通讯作者: 马光辉,e-mail:ghma@ipe.ac.cn E-mail:ghma@ipe.ac.cn
  • 基金资助:
    国家自然科学基金项目（No.21336010，21476241）资助
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Preparation and Application of Porous Polymer Microspheres in Virus-Like Particles Purification

Xiangming Na1,2, Weiqing Zhou1, Juan Li1, Zhiguo Su1, Guanghui Ma1*   

  1. 1. State Key Laboratory Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;
    2. University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2017-09-19 Revised:2017-11-26 Online:2018-01-15 Published:2017-12-13
  • Supported by:
    The work was supported by the National Natural Science Foundation of China(No.21336010, 21476241).
高分子多孔微球在医药领域的分离纯化中应用广泛，是重要的化工产品。高分子多孔微球的形成是一个复杂的过程，利用聚合物与有机溶剂致孔剂的相分离，可得到小于100 nm孔径的多孔微球；而水和疏水性聚合物之间相分离程度远大于有机溶剂与聚合物间的相分离程度，因此可获得大于100 nm孔径的多孔微球。针对不同应用领域选择不同的方法，设计并制备出合理的微球结构，对多孔微球的实际应用十分关键。本综述介绍了纳孔、介孔、大孔微球产品的制备方法悬浮聚合和种子聚合法，重点介绍本课题组制备超大孔微球的方法——反胶团溶胀法和W/O/W复乳法，上述两种方法解决了常规方法难以制备大孔径微球产品的问题，拓展了多孔微球在类病毒颗粒等大尺寸蛋白分离纯化领域的应用。在此基础上，以HB-VLPs为模型对比了不同孔径微球对类病毒颗粒吸附量、回收率、结构、以及纯化效果的差异，揭示超大孔微球产品在类病毒颗粒分离纯化中的优势。
关键词： 高分子多孔微球, 超大孔微球, 类病毒颗粒, 生物大分子分离纯化
Porous polymer microspheres have been widely used in separation and purification of drugs, which are a series of important biochemical engineering products. Formation of porous microspheres is a complex process. Microspheres with pore size below 100 nm is obtained by phase separation of polymers and porogens, while microspheres with pore size above 100 nm can be obtained by phase separation of polymers and water. The porous microspheres with different structures should be delicately designed to meet the application needs. Suspension and seeded polymerizations methods which can be used to fabricate macro-,meso-and nanoporous microspheres are reviewed. Besides, reverse micelles swelling and double emulsion methods are introduced in detail to prepare gigaporous microspheres based on our group's research. HB-VLPs are used to prove the advantages of gigaporous microspheres in biomacromolecules purification by comparison with mesoporous microspheres.
Contents
1 Introduction
2 Suspension polymerization method to prepare porous microspheres
2.1 Using a good solvent as the porogen
2.2 Using a non-solvent as the porogen
2.3 Using solids as the porogen
3 Seeded polymerization method to prepare porous microspheres
4 Reversed micelle swelling method to prepare porous microspheres
5 W/O/W double emulsion method to prepare porous microspheres
6 Application of gigaporous microspheres in virus-like particles purification
6.1 Effect of pore size of microspheres on the adsorption of HB-VLPs
6.2 Effect of pore size of microspheres on the recovery and structure of HB-VLPs
6.3 Actual purif?cation of HB-VLPs on different microspheres
7 Conclusion
Key words: porous microspheres, gigaporous microspheres, virus-like particles (VLPs), separation and purification of biomacromolecules

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