Korean Chemical Engineering Research

The Korean Institute of Chemical Engineers (한국화학공학회)
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Highly Efficient Production of Monodisperse Poly(ethylene glycol) (PEG) Hydrogel Microparticles by Utilizing Double Emulsion Drops with a Sacrificial Thin Oil Shell

얇은 오일쉘 이중에멀젼을 이용한 고효율 단분산성 하이드로젤 마이크로 입자 생산

  • Kim, Byeong-Jin (Division of Cosmetic Science and Technology, Daegu Haany University) ;
  • Jeong, Hye-Seon (Division of Cosmetic Science and Technology, Daegu Haany University) ;
  • Choi, Chang-Hyung (Division of Cosmetic Science and Technology, Daegu Haany University)
  • 김병진 (대구한의대학교 화장품공학부) ;
  • 정혜선 (대구한의대학교 화장품공학부) ;
  • 최창형 (대구한의대학교 화장품공학부)
  • Received : 2021.08.17
  • Accepted : 2021.10.01
  • Published : 2022.02.01
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Abstract

This study reports a microfluidic approach to produce monodisperse hydrogel microparticles in a simple and highly efficient manner. Specifically, we produce double emulsion drops with a thin oil shell surrounding an aqueous prepolymer solution, which is solidified via UV-induced free radical polymerization. When they are dispersed in an aqueous solution, the oil shell is dewetted due to the absence of surfactants, resulting in production of highly uniform hydrogel microparticles (C.V.=1%). Results show that production of monodisperse hydrogel microparticles with controllable size and composition can be achieved with minimal use of oil unlike water-in-oil (w/o) single emulsion-based approach. Furthermore, in-depth study of flow patterns in microfluidic device using a phase diagram exhibits a crucial relationship among relative flow rates while providing windows of readily controllable parameters for reliable manufacturing of hydrogel microparticles.

본 연구는 미세유체기술을 기반으로 매우 간단하고 효율적인 단분산성 하이드로젤 마이크로 입자 제조 방법을 제안하였다. 구체적으로, 유리모세관 미세유체장치 내에서 형성된 이중에멀젼은 자외선기반 자유라디칼 중합에 의해 빠르게 고형화가 이루어진다. 수용액에 분산됨과 동시에 계면활성제의 부족으로 인해 얇은 오일쉘은 자발적으로 분리되어, 단분산성 하이드로젤 입자를 형성하였다(C.V.=1%). 본 연구의 결과는 water-in-oil (w/o) 단일에멀젼 기반의 제조 방법과 달리 오일 부피를 최소한으로 사용하여 크기 및 조성 제어가 가능한 단분산성 하이드로젤 입자의 제조가 달성될 수 있음을 보여준다. 마지막으로, 상도표를 기반으로 미세유체장치 내 유동 패턴에 대한 심층 연구는 상대적인 부피 유속들 간의 중요한 상관관계를 나타내며 하이드로젤 마이크로 입자의 안정적인 제조를 위한 실험적 근거를 제시하였다.

Keywords

Acknowledgement

이 논문은 2018년도 대구한의대학교 기린연구비 지원에 의한 것이며 이에 감사드립니다.

References

  1. Ahmed, E. M., "Hydrogel: Preparation, Characterization, and Applications: A Review," Journal of Advanced Research, 6(2), 105-121(2015). https://doi.org/10.1016/j.jare.2013.07.006
  2. Hoare, T. R. and Kohane, D. S., "Hydrogels in Drug Delivery: Progress and Challenges," Poly., 49(8), 1993-2007(2008). https://doi.org/10.1016/j.polymer.2008.01.027
  3. Oh, J. K., Drumright, R., Siegwart, D. J. and Matyjaszewski, K., "The Development of Microgels/nanogels for Drug Delivery Applications," Progress in Polymer Science, 33(4), 448-477(2008). https://doi.org/10.1016/j.progpolymsci.2008.01.002
  4. Le Goff, G. C., Srinivas, R. L., Hill, W. A. and Doyle, P. S., "Hydrogel Microparticles for Biosensing," European Polymer Journal, 72, 386-412(2015). https://doi.org/10.1016/j.eurpolymj.2015.02.022
  5. Wang, J., Mignon, A., Snoeck, D., Wiktor, V., Van Vliergerghe, S., Boon, N. and De Belie, N., "Application of Modified-alginate Encapsulated Carbonate Producing Bacteria in Concrete: a Promising Strategy for Crack Self-healing," Front Microbiol, 6, 1088-1088(2015). https://doi.org/10.3389/fmicb.2015.01088
  6. Hoffman, A. S., "Hydrogels for Biomedical Applications," Advanced Drug Delivery Reviews, 64, 18-23(2012). https://doi.org/10.1016/j.addr.2012.09.010
  7. Nguyen, K. T. and West, J. L., "Photopolymerizable Hydrogels for Tissue Engineering Applications," Biomaterials, 23(22), 4307-4314(2002). https://doi.org/10.1016/S0142-9612(02)00175-8
  8. Peppas, N. A., Hilt, J. Z., Khademhosseini, A. and Langer, R., "Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology," Advanced Materials, 18(11), 1345-1360(2006). https://doi.org/10.1002/adma.200501612
  9. Shrestha, P., Regmi, S. and Jeong, J.-H., "Injectable Hydrogels for Islet Transplantation: a Concise Review," Journal of Pharmaceutical Investigation, 50(1), 29-45(2020). https://doi.org/10.1007/s40005-019-00433-3
  10. Zhao, C.-X., "Multiphase Flow Microfluidics for the Production of Single or Multiple Emulsions for Drug Delivery," Advanced Drug Delivery Reviews, 65(11), 1420-1446(2013). https://doi.org/10.1016/j.addr.2013.05.009
  11. Li, J. and Mooney, D. J., "Designing Hydrogels for Controlled Drug Delivery," Nature Reviews Materials, 1(12), 16071(2016). https://doi.org/10.1038/natrevmats.2016.71
  12. Du, Y., Lo, E., Ali, S. and Khademhosseini, A., "Directed Assembly of Cell-laden Microgels for Fabrication of 3D Tissue Constructs," Proceedings of the National Academy of Sciences, 105(28), 9522(2008). https://doi.org/10.1073/pnas.0801866105
  13. Hoffmann, J. C. and West, J. L., "Three-dimensional Photolithographic Patterning of Multiple Bioactive Ligands in Poly(ethylene glycol) Hydrogels," Soft Matter, 6(20), 5056-5063(2010). https://doi.org/10.1039/c0sm00140f
  14. Tekin, H., Tsinman, T., Sanchez, J. G., Jones, B. J., Camci-Unal, G., Nichol, J. W., Langer, R. and Khademhosseini, A., "Responsive Micromolds for Sequential Patterning of Hydrogel Microstructures," Journal of the American Chemical Society, 133(33), 12944-12947(2011). https://doi.org/10.1021/ja204266a
  15. Yeh, J., Ling, Y., Karp, J. M., Gantz, J., Chandawarkar, A., Eng, G., Blumling, J., Langer, R. and Khademhosseini, A., "Micromolding of Shape-controlled, Harvestable Cell-laden Hydrogels," Biomaterials, 27(31), 5391-5398(2006). https://doi.org/10.1016/j.biomaterials.2006.06.005
  16. Garstecki, P., Fuerstman, M., Stone, H. and Whitesides, G., "Formation of Droplets and Bubbles in a Microfluidic T-junction - Scaling and Mechanism of Break-up," Lab on a Chip, 6, 437-446(2006). https://doi.org/10.1039/b510841a
  17. Tan, W. H. and Takeuchi, S., "Monodisperse Alginate Hydrogel Microbeads for Cell Encapsulation," Advanced Materials, 19(18), 2696-2701(2007). https://doi.org/10.1002/adma.200700433
  18. Thorsen, T., Roberts, R., Arnold, F. and Quake, S., "Dynamic Pattern Formation in Vesicle-Generating Microfluidic Device," Physical Review Letters, 86, 4163-4166(2001). https://doi.org/10.1103/PhysRevLett.86.4163
  19. Choi, C.-H., Jung, J.-H., Hwang, T.-S. and Lee, C.-S., "In situ Microfluidic Synthesis of Monodisperse PEG Microspheres," Macromolecular Research, 17(3), 163-167(2009). https://doi.org/10.1007/BF03218673
  20. Foster, G. A., Headen, D. M., Gonzalez-Garcia, C., Salmeron-Sanchez, M., Shirwan, H. and Garcia, A. J., "Protease-degradable Microgels for Protein Delivery for Vascularization," Biomaterials, 113, 170-175(2017). https://doi.org/10.1016/j.biomaterials.2016.10.044
  21. Lee, J. N., Park, C. and Whitesides, G. M., "Solvent Compatibility of Poly(dimethylsiloxane)-Based Microfluidic Devices," Analytical Chemistry, 75(23), 6544-6554(2003). https://doi.org/10.1021/ac0346712
  22. Pittermannova, A., Ruberova, Z., Zadrazil, A., Bremond, N., Bibette, J. and Stepanek, F., "Microfluidic Fabrication of Composite Hydrogel Microparticles in the Size Range of Blood Cells," RSC Advances, 6(105), 103532-103540(2016). https://doi.org/10.1039/C6RA23003B
  23. Noudeh, G., Khazaeli, P., Mirzaei, S., Sharififar, F. and S, N., "Determination of the Toxicity Effect of Sorbitan Esters Surfactants Group on Biological Membrane," Journal of Biological Sciences, 9, 423-430(2009). https://doi.org/10.3923/jbs.2009.423.430