얼음입자추출법을 이용한 알부민 함유 PLGA 담체의 제조 및 방출 거동

Preparation and Release Behavior of Albumin-Loaded PLGA Scaffold by Ice Particle Leaching Method

  • 홍금덕 (전북대학교 고분자 나노공학과) ;
  • 서광수 (전북대학교 고분자 나노공학과) ;
  • 김순희 (전북대학교 유기신물질공학과) ;
  • 김선경 (전북대학교 유기신물질공학과) ;
  • 강길선 (전북대학교 고분자 나노공학과, 한국화학연구원 나노생체재료고분자팀) ;
  • 신형식 (전북대학교 화학공학부) ;
  • 김문석 (한국화학연구원 나노생체재료고분자팀) ;
  • 이해방 (한국화학연구원 나노생체재료고분자팀)
  • Hong Keum Duck (Department of Polymer Nano Science and Technology, Chonbuk National University) ;
  • Seo Kwang Su (Department of Polymer Nano Science and Technology, Chonbuk National University) ;
  • Kim Soon Hee (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Kim Sun Kyung (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Khang Gilson (Department Advanced Organic Materials Engineering, Chonbuk National University, Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology) ;
  • Shin Hyung Sik (Department of Chemical Engineering, Chonbuk National University) ;
  • Kim Moon Suk (Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology) ;
  • Lee Hai Bang (Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology)
  • 발행 : 2005.05.01

초록

조직공학적 장기재생에 있어서 필수적 요소인 생분해성 담체를 제조하기 위하여 새로운 방법인 얼음입자추출법을 사용하였다. 형광이 결합된 소 혈청 알부민(bovine serum albumin-fluoiescein isothiocyanate, FITC-BSA)과 락타이드-글리콜라이드 공중합체(PLGA)를 균일하게 혼합한 후에 제조된 얼음입자를 각각 다른 양을 첨가하여 다공성의 담체를 제조하였다. 모델 약물로 이용한 알부민의 방출 실험근 pH 7.4 인산염완충액을 사용하여 $37^{circ}C$, 100 rpm조건으로 항온조에서 28일 동안 수행하였다. 알부민의 방출은 형광 분광기를 통하여 FITC의 강도에 의해 결정되었으며 알부민의 방출 거동에 따른 담체의 형태학적 변화는 전자주사현미경을 이용하여 관찰하였다. 담체를 알부민이 용해된 용액에 단순히 함침시킨 방법에 비해 알부민을 함유하여 제조한 담체의 경우에 초기 방출량이 적고 일정한 방출거동을 보였다. 또한 알부민의 농도에 따른 실험에서 농도가 증가하여도 초기 방출량은 증가하지 않음을 확인할 수 있었다. 본 실험을 통해 PLGA를 이용하여 얼음입자 추출법으로 제조한 담체는 단백질 약물의 서방화가 훌륭하여 생체조직공학적 담체로서 응용 가능함을 확인하였다. 또한, 물 등께 의한 다공물질 추출 과정이 없기 때문에 사이토카인 등과 같은 수용성 인자들의 포접이 용이하여 조직공학적 바이오장기 재생에 유효할 것으로 사료된다.

A novel ice particle leaching method for fabrication of porous and biodegradable PLGA scaffold has been proposed for the application to tissue engineering. After uniform mixing of poly(L-lactide-co-glycolide) (PLGA) and bovine serum albumin-fluorescein isothiocyanate (FITC-BSA), the FITC-BSA loaded scaffold was fabricated by adding various ratio of ice particle. The release profiles of FITC-BSA were examined using pH 7.4 PBS for 28 days at $37^{circ}$. The release amount was determined by fluorescence intensity by using the fluorescence spectrophotometer and the morphological change of the scaffolds was observed by scanning electron microscope. The release initial burst of BSA containing scaffolds was lower than that of simple dipping scaffolds resulting in constant release aspect. Although the BSA concentration increased. the initial burst was not increased. As a result of this study, it can be suggested that ice particle leaching method for the tissue engineered scaffold miff be very useful and it is possible to impregnate with water soluble factors like cytokine. We suggest that ice particle leaching method may be useful to tissue engineered organ regeneration.

키워드

참고문헌

  1. G. Khang and H. B. Lee, 'Cell-synthetic Surface Interaction : Physicochemical Surface Modification', in Methods of Tissue Engineering, A. Atala and R. Lanza, Editors, Academic Press, San Diego, California, Chap. 67, pp 771-780 (2001)
  2. S. J. Lee, G. Khang, Y. M. Lee, and H. B. Lee, J. Biomater. Sci., Polym. Ed., 13, 197 (2002) https://doi.org/10.1163/156856202317414375
  3. G. Khang, S. J. Lee, M. S. Kim, and H. B. Lee, 'Scaffolds : Tissue engineering', in Webster's Biomedical Engineering Handbook, S. Webster, Editor, John & Wiley Press, New York, in press (2005)
  4. G. Khang, M. S. Kim, S. H. Cho, I. Lee, J. M. Rhee, and H. B. Lee, Tissue Eng. Regen. Med., 1, 9 (2004)
  5. G. Khang, S. K. Kim, K. D. Hong, W. Y. Jang, C. W. Han, I. Lee, and H. B. Lee, Tissue Eng., Regen. Med., 1, 136 (2004)
  6. S. P. Baldwin and W. M. Saltzman, Adv. Drug Deliv. Rev., 33, 71 (1998) https://doi.org/10.1016/S0169-409X(98)00021-0
  7. G. Khang, S. J. Lee, C. W. Han, J. M. Rhee, and H. B. Lee, 'Preparation and Characterization of Natural/Synthetic Hybrid Scaffolds', in Advances in Experimental Medicine and Biology, M. Elcin, Editor, Kluwer-Plerum Press, London, Vol 657, Chap. 17, pp 235-245 (2003)
  8. C. W. Patrick, Jr., S. Kukreti, and L. V. Mclntire, Exp. Neurol., 138, 277 (1996) https://doi.org/10.1006/exnr.1996.0066
  9. G. Khang and H. B. Lee, Biomedical Polymers, Korean Chemical Society Press, Munundang, Seoul, 2001
  10. G. Khang, J. M. Rhee, J. K. Jeong, J. S. Lee, M. S. Kim, S. H. Cho, and H. B. Lee, Macromol. Res., 11, 207 (2003) https://doi.org/10.1007/BF03218355
  11. G. Khang, C. S. Park, J. M. Rhee, S. J. Lee, Y. M. Lee, I. Lee, M. K. Choi, and H. B. Lee, Korea Polym. J., 9, 267 (2001)
  12. G. Khang, M. K. Choi, J. M. Rhee, S. J. Lee, and H. B. Lee, Korea Polym. J., 9, 107 (2001)
  13. S. J. Lee, G. Khang, Y. M. Lee, and H. B. Lee, J. Biomater. Sci., Polym. Ed., 13, 197 (2002) https://doi.org/10.1163/156856202317414375
  14. G. Khang, C. W. Choee, J. M. Rhee, and H. B. Lee, J. Appl. Polym. Sci., 85, 1253 (2002) https://doi.org/10.1002/app.10680
  15. G. Khang, P. Shin, I. Kim, B. Lee, S. J. Lee, Y. M. Lee, H. B. Lee, and I. Lee, Macromol. Res., 10, 158 (2002) https://doi.org/10.1007/BF03218266
  16. Y. Iwasaki, S. Sawada, N. Nakabayashi, G. Khang, H. B. Lee, and K. Ishihara, Biomaterials, 23, 3877 (2002)
  17. S. A. Seo, J. H. Kim, G. Khang, J. M. Rhee, and H. B. Lee, J. Microencapsulation, 20, 569 (2003)
  18. G. Khang, E. K. Jeon, J. M. Rhee, I. Lee, S. J. Lee, and H. B. Lee, Macromol. Res., 11, 334 (2003) https://doi.org/10.1007/BF03218373
  19. S. K. Kim, K. D. Hong, J. W. Jang, S. J. Lee, M. S. Kim, C. W. Han, G. Khang, I. Lee, and H. B. Lee, Tissue Eng., Regen. Med., 1, 149 (2004)
  20. H. S. Choi, G. Khang, H. Shin, J. M. Rhee, and H. B. Lee, Int. J. Pharm., 234, 195 (2002) https://doi.org/10.1016/S0378-5173(01)00968-1
  21. S. A. Seo, H. S. Choi, G. Khang, J. M. Rhee, and H. B. Lee, Int. J. Pharm., 239, 93 (2002) https://doi.org/10.1016/S0378-5173(02)00074-1
  22. M. Penco, S. Marchioni, P. Ferruti, S. D'antone, and P. Deghenghi, Biomaterials, 17, 1583 (1996) https://doi.org/10.1016/0142-9612(95)00323-1
  23. S. J. Holland, B. J. Tighe, and P. L. Gould, J. Controlled Release, 4, 155 (1986) https://doi.org/10.1016/0168-3659(86)90001-5
  24. L. E. Freed, J. C. Marquis, A. Nohria, J. Emmanual, A. G. Mikos, and R. Langer, J. Biomed. Mater. Res., 11, 27 (1993)
  25. J. W. Jang, B. Lee, C. W. Han, I. Lee, H. B. Lee, and G. Khang, Polymer(Korea), 27, 226 (2003)
  26. G. Khang, J. H. Jeon, J. C. Cho, and H. B. Lee, Polymer(Korea), 23, 3 (1999)
  27. J. H. Aubert and R. L. Clough, Polymer, 26, 2047 (1985) https://doi.org/10.1016/0032-3861(85)90186-7
  28. D. J. Mooney, C. L. Mazzoni, C. Breuer, K. McNamara, D. Hem, J. P. Vacanti, and R. Langer, Biomaterials, 17, 115 (1996) https://doi.org/10.1016/0142-9612(96)85756-5
  29. I. Y. Kim, J. W. Jang, B. Lee, S. J. Lee, J. H. Choee, H. B. Lee, and G. Khang, Macromol. Chem. Symp., 15, 141 (2002)
  30. K. Whang, T. K. Goldstick, and K. E. Healy, Biomaterials, 21, 2545 (2000) https://doi.org/10.1016/S0142-9612(00)00122-8
  31. K. Whang, C. H. Thomas, and K. E. H. Nuber, Polymer, 36, 837 (1995) https://doi.org/10.1016/0032-3861(95)93115-3
  32. K. Whang, K. E. Healy, D. R. Elenz, E. K. Nam, D. C. Tsai, C. H. Thomas, G. W. Nuber, F. H. Glorieux, and R. Travers, Tissue Eng., 5, 35 (1999) https://doi.org/10.1089/ten.1999.5.35
  33. N. Moriah and S. Lonnie, J. Biomed. Mater. Res., 59, 349 (2002) https://doi.org/10.1002/jbm.1251
  34. A. M. Ambrosio, J. S. Sahota, Y. Khan, and C. T. Laurencin, J. Biomed. Mater. Res., 58, 295 (2001) https://doi.org/10.1002/1097-4636(2001)58:1<1::AID-JBM10>3.0.CO;2-8
  35. A. P. Marques, R. L. Reis, and J. A. Hunt, Biomaterials, 23, 1471 (2002) https://doi.org/10.1016/S0142-9612(01)00272-1
  36. K. S. Seo, M. S. Kim, K. Kim, S. H. Cho, H. B. Lee, and G. Khang, Polymer(Korea), 28, 328 (2004)
  37. G. Chen, T. Ushida, and T. Tateishi, Mater. Sci. Eng. C, 17, 63 (2001) https://doi.org/10.1016/S0928-4931(01)00324-1
  38. G. Chen, T. Ushida, and T. Tateishi, Biomaterials, 22, 2563 (2001) https://doi.org/10.1016/S0142-9612(00)00074-0