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Effects of process parameters on encapsulations of BSA aqueous solutions into PLGA microcapsule particles using double emulsion technique

이중유화법을 통하여 BSA 수용액을 PLGA 마이크로캡슐 입자에 봉입하는 과정에서의 공정변수의 영향

  • Kwon, Sejin (School of Energy-Materials-Chemical Engineering, Korea University of Technology and Education) ;
  • Koo, Ja-Kyung (School of Energy-Materials-Chemical Engineering, Korea University of Technology and Education)
  • 권세진 (한국기술교육대학교 에너지-신소재-화학공학부) ;
  • 구자경 (한국기술교육대학교 에너지-신소재-화학공학부)
  • Received : 2018.05.02
  • Accepted : 2018.06.01
  • Published : 2018.06.30

Abstract

PLGA microcapsule particles encapsulating BSA aqueous solutions were prepared using a water-in-oil-in-water emulsion method. The morphology, particle size, BSA encapsulating efficiency, and in-vitro release test were also studied using the microcapsule particles. In the outer aqueous phase, an emulsifier, e.g., PVA, was replaced with metal salts for surface solidification. Scanning electron microscopy (SEM) showed that the microcapsule particles had smooth surfaces and were between $1{\mu}m$ and $7{\mu}m$ in size. The microcapsule particle morphology was affected directly by the ratio between the polymer solution and inner aqueous solution, and composition of the outer aqueous solution. The factors also partially affected the BSA encapsulation efficiencies and in-vitro release rates. All the microcapsule particles showed an initial burst release through the in-vitro release test. On the other hand, the particles also showed a relatively long release period. Metal salts could be good choices to replace the emulsifier to solidify the microcapsule particle surfaces.

이중유화법을 통하여 BSA 수용액을 봉입하는 PLGA 마이크로캡슐 입자를 제조하였다. 마이크로캡슐 입자 외부의 수용액 상에서는 입자 표면의 경화를 위하여 유화제를 금속염으로 대체하였다. 제조한 마이크로캡슐 입자에 대하여서 모폴로지, 입자직경 BSA 봉입효율 및 in-vitro 방출실험을 수행하였다. 전자현미경(SEM) 촬영을 통하여 마이크로캡슐 입자는 매끄러운 표면의 특성을 지녔으며 $1-7{\mu}m$ 범위의 직경을 갖는 것이 확인되었다. 마이크로캡슐 입자의 모폴로지는 주로 일차 유화액 내 내부 수용액 대비 고분자 용액의 부피 비 그리고 입자 외부 수용액에서의 금속염의 농도에 직접적인 영향을 받았다. 또한 이러한 요소는 단백질 봉입효율과 in-vitro 방출에도 일부 영향을 미쳤다. 본 실험에서 제조한 마이크로캡슐 입자는 in-vitro 방출 실험에서 초기에 높은 유속의 방출 현상을 보였다. 그렇지만 본 연구에서 제조한 마이크로캡슐 입자는 다른 연구의 결과에 비해 긴 기간 동안의 방출을 보였다. 이상의 결과를 통해 2가의 금속염이 마이크로캡슐 입자의 제조에서 유화제를 대체할 수 있는 좋은 방편이 될 수 있다는 결론을 내릴 수 있었다.

Keywords

References

  1. Y. Wei, Y.X. Wang, W. Wang, S.V. Ho, F. Qi, G.H. Ma, Z.G. Su, "Microcosmic mechanisms for parotein incompetable release and stability of various amphiphilic PEG-PLA microspheres", Langmuir, vol. 28, no. 39, pp. 13984-13992, 2012. DOI: https://doi.org/10.1021/la3017112
  2. W. Wang, M.J. Zhang, R. Xie, X.J. Ju, C. Yang, C.L. Mou, D.A. Weitz, L.Y. Chu, "Hole-shell microparticles from controllably evaporated double emulsions", Angew. Chem. Int. Ed., vol. 52, no. 31, pp. 8084-8087, 2013. DOI: https://doi.org/10.1002/anie.201301590
  3. Q.X. Xu, S.H. Chin, C.H. Wang, D.W. Pac, "Mechanism of durg release from double-walled PDLLA-PLGA microspheres", Biomaterials, vol. 34, no. 15, pp. 3902-3911, 2013. DOI: https://doi.org/10.1016/j.biomaterials.2013.02.015
  4. Y. Cho, Y. Kim, J-K. Koo, J-S Park, "Effect of solvent on the fabrication of poly(L-lactide) scaffold membranes through phase inversion", Membrane J., vol. 24, no. 2, pp. 113-122, 2014. DOI: https://doi.org/10.14579/MEMBRANE_JOURNAL.2014.24.2.113
  5. Y. Cho, Y. Kim, J-K. Koo, "Fabrication of poly(L-lactide) scaffold membranes through phase inversion with mixed solvents", Membrane J., vol. 25, no. 1, p48-59, 2015. DOI: https://doi.org/10.14579/MEMBRANE_JOURNAL.2015.25.1.48
  6. G. Xu, X. Liu, J. Xu, L. Li, H. Su, H. Zhao, H. Fang, "High flux nanofiltration membranes based on layer-by-layer assembly modified electrospun nanofibrous substrate", Appl. Surf. Sci., 434, pp. 573-581, 2018. DOI: https://doi.org/10.1016/j.apsusc.2017.10.188
  7. J.B. Dou, Q.Y. Zhang, M.L. Ma, J.W. Gu, "Fast fabrication of epoxy-functionalized magnetic polymer core-shell microspheres using glycidyl methacrylate as monomer via photo-initiated polymerization", J. Magn. Mater., vol. 324, no. 19, pp. 3078-3082, 2012. DOI: https://doi.org/10.1016/j.jmmm.2012.05.005
  8. L. Wang, H. Liang, F. Wang, L.Y. Huang, Z.P. Liu, Z.X. Dong, "One-step synthesis of uniform double-shelled polystyrene/poly(o-toluidine) composite hollow spheres", Langmuir, vol. 29, no. 19, pp. 5863-5868, 2013. DOI: https://doi.org/10.1021/la401329d
  9. J. Wu, T.T. Kong, K.W.K. Yeung, H.C. Shum, K.M.C. Cheung, and L.Q. Wang, "Fabrication of monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells for controlled drug release", Acta Biomater., vol. 9, no. 7, pp. 7410-7419, 2013. DOI: https://doi.org/10.1016/j.actbio.2013.03.022
  10. Y. Sato, Y. Kawashima, H. Takeuchi, H. Yamamoto, "Physicochemical properties to determine the buoyancy of hollow microspheres(microballoons) prepared by the emulsion solvnet diffusion method", Eur. J. Pharm. Biopharm., vol. 55, no. 3, pp. 297-304, 2003. DOI: https://doi.org/10.1016/j.actbio.2013.03.022
  11. B. Albuquerque, M.S. Costa, I.N. Peca, M.M. Cardoso, "Production of double-walled nanoparticles containing meloxicam", Polym. Eng. Sci., vol. 53, no. 1, pp. 146-152. 2013. DOI: https://doi.org/10.1002/pen.23256
  12. S.K. Sahoo, J. Panyam, S. Prabha, V. Labhasetwar, "Residual polyvinyl alcohol associated with poly(D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake", J. Control. Release, vol. 82, no. 1, pp. 105-114, 2002. DOI: https://doi.org/10.1016/S0168-3659(02)00127-X
  13. Q. Wang, H. Hu, A. Zoghbi, J. Huang, Q. Xia, "Oil-in-oil-in water pre double emulsions stablized by nonionic surfactants and silica particles:A new approach for torical application fo rutin", Colloid. Surface A, 522, pp. 399-407, 2017. DOI: https://doi.org/10.1016/j.colsurfa.2017.02.067
  14. M.D. Blanco, M.J. Alonso, "Development and characterization of proteinloaded poly(lactide-co-glycolide) nanospheres", Eur. J. Pharm. Biopharm, 43, pp. 287-294, 1997. DOI: https://doi.org/10.1016/S0939-6411(97)00056-8
  15. E. Cohen-Sela, M. Chorny, N. Koroukhov, H.D. Danenberg, G. Golomb, "A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles", J. Control. Release., vol. 133, no. 2, pp. 90-95, 2009. DOI: https://doi.org/10.1016/j.jconrel.2008.09.073
  16. F. Han, F. Zhou, X. Yang, J. Zhao, Y. Zhao, Z. Yuan, "Facile preparation of PLGA microspheres with diverse internal structures by modified double-imulsion method for controlled release", Polym. Eng. Sci. 55(4) pp. 896-905, 2015 DOI: https://doi.org/10.1002/pen.23957
  17. M. Polakovic, T. Gorner, R. Gref, E. Dellacherie, "Lidocaine loaded biodegradable nanospheres:II. modelling of drug release", J. Control. Release, vol. 60, no. 2, pp. 169-177, 1999. DOI: https://doi.org/10.1016/S0168-3659(99)00012-7
  18. H. Y. Zhou, X. G. Chen, C. S. Liu, X. H. Meng, C. G. Liu and L. J. Yu, "Release characteristics of three model drugs from chitosan/cellulose acetate multimicrospheres", Biochem. Eng. J., 31, pp. 228-233, 2006. DOI: https://doi.org/10.1016/j.bej.2006.08.007