Preparation and Characterization of Microparticles of $Poly(\gamma-glutamic\;acid)$ Containing Lysozyme by means of Supercritical Anti-Solvent (SAS) Precipitation Process

초임계 반용매 침전법에 의한 라이소자임이 내포된 폴리감마글루탐산의 미세입자 제조 및 특성

  • Lee, Dong-Il (Department of Polymer Science and Engineering, Kumoh National Institute of Technology) ;
  • Ling, Yun (Department of Polymer Science and Engineering, Kumoh National Institute of Technology) ;
  • Sung, Moon-Hee (Department of Chemistry, Kookmin University) ;
  • Park, Il-Hyun (Department of Polymer Science and Engineering, Kumoh National Institute of Technology)
  • 이동일 (금오공과대학교 고분자공학과) ;
  • 능운 (금오공과대학교 고분자공학과) ;
  • 성문희 (국민대학교 화학과) ;
  • 박일현 (금오공과대학교 고분자공학과)
  • Published : 2007.03.31

Abstract

The sub-micron particles of poly ($\gamma-glutamic$ acid) (PGA) containing lysozyme have been prepared using supercritical antisolvent (SAS) precipitation process at various experimental conditions such as pressure, temperature, inner diameter of nozzle, and concentration. As overall results of the application of SAS process to this system, the smaller size powder has been produced as (i) increasing pressure, (ii) decreasing temperature, (iii) decreasing the inner diameter of nozzle, and (iv) decreasing the concentration of PGA and lysozyme. It is found by means of FT-IR analysis that during SAS process, the composition has changed from the original composition of PGA : lysozyme=50 : 50 into PGA : lysozyme=33 : 67 at final product powder. It means that PGA has higher solubility for the mixed solvent of carbon dioxide and dimethyl sulfoxide (DMSO). Due to such difference of solubility, this particle forms the core-shell structure of which the core consists mainly of lysozyme. It is also found that the residual DMSO amount of $7.8\times10^{-3}wt%$ exists inside the powder.

라이소자임이 내포된 폴리감마글루탐산(PGA)의 서브-마이크론 크기의 미세입자를 압력, 온도, 노즐내경, 농도 등을 변화시켜가면서 초임계 반용매 침전법 (SAS)으로 제조하였다. SAS법의 전체적인 결과는 압력이 클수록, 온도가 낮을수록, 노즐 내경이 작을수록, 농도가 묽을수록 작은 입자가 얻어졌다. FT-IR로 분석한 결과, 본래 초기의 PGA:라이소자임:50 : 50의 조성비는 SAS 공정을 거치면서 최종 분말 입자 내에서는 33 : 67로 변화하였다. 이것은 PGA가 라이소자임보다 탄산가스/디메틸설폭사이드(DMSO) 혼합용매에 더 높은 용해도를 가지기 때문인 것으로 추측된다. 또 이러한 용해도 특성 때문에 생성 입자는 핵-껍질 구조를 갖고 있으며, 핵 부분은 라이소자임이 구성하는 것으로 여겨진다. 생성된 분말 입자 내에는 $7.8\times10^{-3}wt%$의 농도로 미량의 DMSO가 잔존하고 있음이 밝혀졌다.

Keywords

References

  1. E. Reverchon, J. Supercrit. Fluids, 15, 1 (1999)
  2. E. Reverchon, G. Della Porta, A. Di Trolio, and S. Pace, Ind. Eng. Chem. Res., 37, 952 (1998) https://doi.org/10.1021/ie9704814
  3. E. Reverchon, G. Della Porta, D. Sannino, and P. Ciambelli, Powder Technol., 102, 127 (1999)
  4. Y. Gao, T. K. Mulenda, Y.-F. Shi, and W.-K. Yuan, J. Supercrit. Fluids, 13, 369 (1998)
  5. R. B. Gupta and J.-J. Shim, Solubility in Supercritical Carbon Dioxide, CRC, New York, 2006
  6. E. Reverchon, R. Adami, I. De Marco, C. G. Laudani, and A. Spada, J. Supercrit. Fluids, 35, 76 (2005) https://doi.org/10.1016/j.supflu.2004.10.010
  7. D. H. Kim, H. J. Park, S. H. Kang, S. W. Jun, M. S. Kim, S. Lee, J. S. Park, and S. J. Hwang, J. Kor. Pharm. Sci., 35, 89 (2005)
  8. H. J. Park, M. S. Kim, S. Lee, J. S. Kim, J. S. Woo, J. S. Park, and S. J. Hwang, Int. J. Pharm., 328, 152 (2007) https://doi.org/10.1016/j.ijpharm.2006.08.005
  9. A. Vatanara, R. Najafabadi, K. Gilani, R. Asgharian, M. Darabi, and M. Rafiee-Tehrani, J. Supercrit. Fluids, 40, 111 (2007) https://doi.org/10.1016/j.supflu.2006.03.028
  10. I. Tsivintzelis, E. Pavlidou, and C. Panayiotou, J. Supercrit. Fluids, 40, 317 (2007) https://doi.org/10.1016/j.supflu.2006.06.001
  11. A. Tenorio, M. D. Gordillo, C. Pereyra, and E. J. Martinez de la Ossa, J. Supercrit. Fluids, 40, 308 (2007) https://doi.org/10.1016/j.supflu.2006.07.003
  12. R. B. Gupta and P. Chattopadhyay, U.S. Patent Application 60/206,644 (2000)
  13. P. Chattopadhyay and R. B. Gupta, AIChE, J., 48, 235 (2002) https://doi.org/10.1002/aic.690480102
  14. M. J. Whitaker, J. Hao, O. R. Davies, G. Serhatkulu, S. Stolnik-Trenkic, S. M. Howdle, and K. M. Shake sheff, J. Control. Release, 101, 85 (2005) https://doi.org/10.1016/j.jconrel.2004.07.017
  15. R. Bodmeier, H. Wang, D. J. Dixon, S. Mawson, and K. P. Johnston, J. Pharm. Res., 13, 1211 (1995)
  16. E. Reverchon, G. Della Porta, C. Celano, S. Pace, and A. Di Trolio, J. Mater. Res.,13, 284 (1998)
  17. Yun Ling, Master Thesis, Kumoh National Institute of Technology, 2004
  18. A. Kordikowski, A. P. Schenk, R. M. Van Nielen, and C. J. Peters, J. Supercrit. Fluids., 8, 205 (1995)
  19. S. D. Yeo, G. B. Lim, P. G. Debenedetti, and H. Bernstein, Biotech. Bioeng., 41, 341 (1993)
  20. E. Reverchon, I. De Marco, G. Caputo, and G. Della Porta, J. Supercrit. Fluids, 26, 1 (2003) https://doi.org/10.1016/S0896-8446(02)00186-9
  21. S. Mawson, S. Kanakia, and K. P. Johnston, J. Appl. Polym. Sci., 64, 2105 (1997)
  22. D. Verhamme, J. Storck, L. Racchelli, and A. Lauwers, Int. J. Pharm., 2, 168 (1988)