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  English.dicp.cas.cn    Posted:2017-03-15
Microspheres and microcapsules in Biotechnology: design, preparation, and applications

Time: Mar. 15, 2017 10:00 AM

Conference Room on the First Floor, Basic Energy Building

Guanghui Ma,

Director of State Key Laboratory of Biochemical Engineering

Institute of Institute of Process Engineering, Chinese Academy of Sciences

Microspheres and microcapsules have important applications in biochemical engineering and pharmaceutical engineering, such as enzyme immobilization, protein separation and purification, controlled drug release. Traditionally, most microspheres and microcapsules are produced by mechanical stirring-sieving method. During this process, the oil-in-water (or water-in-oil) emulsion can be prepared by mixing and dispersing in a stirred tank, and then the microspheres or microcapsules can be formed by physically or chemically solidifying the emulsion droplets. As the size of the emulsion is widely distributed, the microspheres or microcapsules obtained after solidification is not uniform. Therefore, repeated screen process is required to obtain the desired particle size, resulting in waste of raw materials and energy. In addition, this screen process often requires a lot of solvent, causing environmental pollution.

To solve this problem, we utilized the microporous membrane to replace the dispersion method in the stirred tank. The dispersed phase was pressed through the uniform pores of the membrane into a continuous phase to form the uniform emulsion droplets. Through a large number of theoretical and experimental studies, we demonstrated that when the dispersed phase and membrane interfacial tension, transmembrane pressure and continuous phase of the drag force became balanced, the droplet would automatically fall off from the membrane surface. By controlling the interface between the dispersion and the interface tension and the droplet formation speed, uniform sized droplets could be obtained, thus overcoming the key issue of droplets preparation via traditional mechanical mixing method. By choosing different pore size of microporous membrane, uniform emulsions of different sizes could be prepared. After physical or chemical solidification method, uniform microspheres or microcapsules could subsequently be obtained. We first developed the membrane emulsification process to prepare O/W (oil in water) emulsion and obtained uniform hydrophobic microspheres. We then extended this technique to the W/O/W and O/W/O double emulsion system, and successfully prepare chitosan microspheres, polylactic acid microcapsules and chitosan microcapsules for drug loading. Using the uniform porous polystyrene microspheres as the column separation media, the natural products were isolated and purified, and the uniformity of the particle size was found to greatly improve the separation of the active components and the impurities of the analogs, thus improving the recovery and purity of the products. We also used the uniform agarose microspheres as the chromatographic separation media for high protein separation resolution. Furthermore, by using uniform polylactic acid microcapsules for long-acting protein drug carrier, uniform particle size ensured the batch repeatability and the reproducibility of drug release. In addition, uniform chitosan microspheres were used to encapsulate the protein/peptide drug, which ensured the systematic study of evaluating the effect of particle size and morphology on the efficacy of orally administrated drug. Finally, recent progress of using uniform microspheres as anti-vaccine separation media, vaccine delivery system (vaccine adjuvant), anti-cancer drug delivery system research results are also introduced.

Prof. Guanghui Ma

Institute of Institute of Process Engineering

 1998 B.E. of Gunma University, Japan

 1993 M.E. & Ph.D. of Tokyo Institute of Technology, Japan

 2001 Winner of National Science Fund for Distinguished Young Scholars, Institute of Institute of Process Engineering

 Present Director of State Key Laboratory of Biochemical Engineering, vice president of Chinese Society of Particuology, vice chairman of Biochemical Engineering Committee in Chemical Industry and Engineering Society of China, and editorial member of J Microencapsul.

Prof. Ma’s research areas are biochemical engineering that focus on innovative research and application of microspheres and microcapsules. She established the microporous membrane emulsification technique to solve the problem of un-uniform sized microspheres sourced from traditional preparation method. Moreover, she proposed and established the preparation method of uniform microspheres with small size in high viscosity polysaccharide system. She also explored several new functions of polysaccharide microspheres including the autofluorescence property, environmental sensitive response, and crystallization control. In addition, theoretical and technology platform of microspheres and microcapsule have been successfully established for the separation media, drug carriers and vaccine adjuvants, which contributed a lot to the development of bio-separation and bio-formulation. To date, Prof. Ma has published 334 papers (167 first/communication author), such as the Nature Commun, JACS, Angew Chem Int Ed, Adv Materials, ACS Nano, Biomaterials and other important international academic journals. The total citation number is 5560 (SCI citation 5011). She won 3 times of the Elsevier reference award, edited or wrote 11 English book/monograph, such as "Microspheres and Microcapsules in Biotechnology", "polymer microsphere material". She is also an invited editor for three special issue of SCI journals (e.g. "Small" and "Vaccine"). She is also an invited speaker of the Gordon Research Conference and the chief of the 2ed and 5th Asian Association of Polymer Microspheres.

She has closely linked the fundamental study and transform applications. She has many collaborate work with the United States General Electric Health Group (GE), the United Kingdom Unilever, Hualan biological and other well-known enterprises. She has been authorized 82 Chinese invention patent and 6 international patent. One patent has been transferred to the world's largest bio-microsphere manufacturing company GE, which developed to a series of commercialized products in the world.

Awards:

 2005 First Prize of Beijing Science and Technology Award

 2009 Second Prize of National Technology Invention Award (uniform size, controllable emulsion, microspheres and microcapsule preparation technology)

 2009 Elsevier Young Female Researcher Award (The Third World Academy of Sciences - the third world Women's Science Organization)

 2012 Asian Biotechnology Association Outstanding Contribution Award

 2014 Hou Diping Chemical Technology Innovation Award

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