화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.28, No.3, 232-238, May, 2004
Export Citation
이식형 단백질 전달체로서 메톡시 폴리(에틸렌 글리콜)/폴리카프로락톤 블록 공중합체의 합성 및 알부민의 방출 거동
Synthesis of Methoxy Poly(ethylene glycol)-b-poly(ε-caprolactone) Diblock Copolymers and Release Behavior of Albumin for Implantable Protein Carriers
서광수, 전세강1, 김문석2, 조선행2, 이해방2, 강길선†
  • 전북대학교 고분자ㆍ나노공학과
  • 1전북대학교 유기신물질공학과
  • 2한국화학연구원 나노생체재료연구팀
Kwang Su Seo, Se Kang Chon1, Moon Suk Kim2, Sun Hang Cho2, Hai Bang Lee2, and Gilson Khang†
  • Department of PolymerㆍNano Science and Technology, Chonbuk National University, 664-14, Dukjin Ku, Jeonju 561-756, Korea
  • 1Department of Advanced Organic Materials Engineering, Chonbuk national University, 664-14, Duckjin Gu, Jeonju, 561-756, Korea
  • 2Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P.O.Box 107, Yuseong, Daejon 305-506, Korea
E-mail:
초록
약물 전달체로서 메톡시 폴리(에틸렌 글리콜) (MPEG, methoxypolyethylene glycol)과 생분해성 폴리에스테르 계열의 카프로탁톤 (ε-CL, ε-caprolactone)으로 구성된 MPEG-PCL 블록 공중합체를 개환중합을 통해 합성하였다. MPEG-PCL의 결정성과 열적특성은 X선 굴절계와 시사주차열량계를 통하여 분석하였다. 모델 단백질로서 알부민(FITC-BSA, albumin bovine-fluorescein isothiocyanate)과 블록 공중합체를 동결 제분 후, 직접 압축 성형방법에 의해 웨이퍼를 제조하였다. 알부민의 방출은 pH 7.4 인산염완충액을 사용하여 37 ℃에서 14일 동안 관찰하였다. 알부민의 방출양은 형광분광기를 통하여 FITC의 강도에 의해 결정되었다. 웨이퍼의 형태학적 관찰은 디지털 카메라와 전자주사현미경을 통하여 관찰하였다. 알부민의 방출 속도와 초기 burst는 MPEG-PCL 블록 공중합체의 분절 내에서 폴리(에틸렌 글리콜)의 분자량이 증가할수록 또한 폴리카프로락톤의 분자량이 감소할수록 많은 초기방출과 단축된 방출기간을 보였다.
MPEG-PCL diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and ε-caprolactone (CL) as drug carriers were synthesized by ring-opening polymerization. MPEG-PCL diblock copolymers were characterized by X-ray diffraction and differential scanning calorimetry. After freeze milling of block copolymers and albumin bovine-fluorescein isothiocyanate (FITC-BSA) as model protein, the wafers loaded FITC-BSA were fabricated by direct compression method. The release profiles of FITC-BSA were examined using pH 7.4 PBS for 14 days at 37 ℃. The release amount was determined by fluorescence intensity by using the fluorescence spectrophotometer. The morphological change of wafers was observed by digital cameraand scanning electron microscope. The release rate and initial burst of BSA increased with increasing PEG molecular weights and decreasing PCL molecular weights in the segments of MPEG-PCL diblock copolymers.
Keywords:implantable protein carrier;MPEG-PCL;FITC-BSA;long-term delivery;biodegradable
  1. Panyam J, Labhasetwar V, Adv. Drug. Deliv. Rev., 55, 329 (2002)
  2. Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V, Faseb J., 16, 1217 (2002) 
  3. Igartua M, Hernandez RM, Esquisabel A, Gascon AR, Calvo MB, Pedraz JL, J. Microencapsul., 14(3), 349 (1997)
  4. Coombes AG, Yeh MK, Lavelle EC, Davis SS, J. Control. Release, 52, 311 (1998) 
  5. Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Korea Polym. J., 7(2), 79 (1999)
  6. Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., 9, 49 (1999)
  7. Lee HB, Khang G, Cho JC, Rhee JM, Lee JS, Polym. Prepr., 40, 288 (1999)
  8. Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
  9. Cho JC, Khang G, Choi HS, Rhee JM, Lee HB, Polym.(Korea), 24(5), 728 (2000)
  10. Khang G, Choi HS, Rhee JM, Yoon SC, Cho JC, Lee HB, Korea Polym. J., 8(6), 253 (2000)
  11. Son WI, Yun DI, Khang G, Kim BS, Lee HB, Biomater. Res., 4, 92 (2000)
  12. Choi HS, Kim SW, Yun DI, Khang G, Rhee JM, Kim YS, Lee HB, Polym.(Korea), 25(3), 334 (2001)
  13. Seong HS, Moon DS, Khang G, Lee HB, Macromol. Chem. Phys., 4, 95 (2001)
  14. Seo SA, Choi HS, Lee DH, Khang G, Lee HB, Polym.(Korea), 25(6), 884 (2001)
  15. Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002) 
  16. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  17. Seo SA, Choi HS, Khang G, Rhee JM, Lee HB, Int. J. Pharm., 239, 93 (2002) 
  18. An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
  19. Yoo JY, Kim SW, Khang G, Seong HS, Jeong JK, Kim HJ, Lee JS, Lee HB, Polym.(Korea), 26(5), 680 (2002)
  20. Khang G, Lee HB, Chap. 67, Cell-synthetic Surface Interaction: Physicochemical Surface Modification, Section II. Methods for Cell Delivery Vehicles, In Methods of Tissue Engineering, A. Atala and R. Lanza Eds., Academic Press, pp. 771-780 (2001)
  21. Lee SJ, Khang G, Lee YM, Lee HB, J. Biomater. Sci.-Polym. Ed., 13, 197 (2002) 
  22. Khang G, Park CS, Rhee JM, Lee SJ, Lee YM, Choi MK, Lee HB, Lee I, Korea Polym. J., 9(5), 267 (2001)
  23. Mergaert J, Ruffieux K, Bourban C, Storms V, Wagemans W, Wintermantel E, Swings J, J. Polym. Environ., 8, 17 (2000) 
  24. Chen DR, Bei JZ, Wang SG, Polym. Degrad. Stabil., 67, 455 (2000) 
  25. Jagur-Grodzinski J, React. Funct. Polym., 39(2), 99 (1999) 
  26. Masahiko O, Prog. Polym. Sci., 27, 87 (2002) 
  27. Chiellini E, Solaro R, Adv. Mater., 8, 305 (1996) 
  28. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM, Chem. Rev., 99(11), 3181 (1999) 
  29. Robert L, Science, 260, 920 (1993) 
  30. Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997) 
  31. Lowery KJ, Hamson KR, Bear L, Peng YB, Celaluce R, Evans ML, Anglen OJ, Allen WC, J. Biomed. Mater. Res., 36, 536 (1997) 
  32. Zhang L, Chu CC, Loh IH, J. Biomed. Mater. Res., 27, 1425 (1993) 
  33. Strock M, Orend KH, Schmitzrixen T, Vasc. Surg., 27, 413 (1993)
  34. Merrill EW, Salzman EW, J. Am. Soc. Artif. Intern. Organs, 6, 60 (1983)
  35. Lee JH, Kopecek J, Andrade JD, J. Biomed. Mater. Res., 23, 351 (1989) 
  36. Mallarde D, Boutignon F, Moine F, Barre E, David S, Touchet H, Ferruti P, Deghenghi R, Int. J. Pharm., 261, 69 (2003) 
  37. Cleland JL, Pharm. Biotechnol., 10, 1 (1997)
  38. Jain R, Rhodes CT, Railkar AM, Malick AW, Shah NH, Eur. J. Pharm. Biopharm., 50, 257 (2000) 
  39. Jain R, Shah NH, Malick AW, Rhodes CT, Drug. Develop. Ind. Pharm., 24, 703 (1998)
  40. Medlicott NJ, Tucker IG, Adv. Drug Deliv. Rev., 38, 139 (1999) 
  41. Shibasaki Y, Sanada H, Yokoi M, Sanda F, Endo T, Macromolecules, 33(12), 4316 (2000)