• Synthesis of Thermosensitive and Biodegradable Methoxy Poly(ethylene glycol)-Polycaprolactone and Methoxy Poly(ethylene glycol)-Poly(lactic acid) Block Copolymers
  • Seo KS, Park CS, Kim MS, Cho SH, Lee HB, Khang G
  • 온도감응 및 생분해성 폴리에틸렌 글리콜-폴리카프로락톤과 폴리에틸렌 글리콜-폴리락타이드 공중합체의 합성
  • 서광수, 박종수, 김문석, 조선행, 이해방, 강길선
Abstract
The sol to gel transition of aqueous solution of block copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and biodegradable polyesters such as ε-caprolactone and L-lactide was investigated as a function of temperature. MPEG-PCL was prepared by ring opening polymerization of ε-caprolactone in the presence of HCl·Et2O as monomer activator at room temperature. Also, MPEG-PLLA was prepared by ring opening polymerization of L-lactide in the presence of stannous octoate at 115 ℃. The properties of block copolymers were investigated by 1H-NMR, IR, and GPC as well as the observation of thermosensitive phase transition in aqueous solution. As the hydrophobic block length increased, the sol to gel transition temperature increased and curve of that steepen to lower concentration. To confirm the gel formation at body temperature, we observed the formation of gel in the mice body after injection of 20 wt% aqueous solution of each block copolymer. After surging, we investigated the gelation in mice. The results obtained in this study confirmed the feasibility as biomaterials of injectable implantation for controlled release of drug and protein delivery.

메톡시 폴리(에틸렌 글리콜)과 생분해성 폴리에스테르 계열의 카프로락톤 그리고 락타이드로 구성된 블록 공중합체를 수용액 상에서 온도에 따른 솔-겔 전이 현상을 연구하였다. 폴리(에틸렌 글리콜)-폴리카프로락톤(MPEG-PCL)은 HCl·Et2O 촉매 존재하에서 실온에서 반응 용매로서 메틸렌클로라이드를 사용하여 카프로락톤의 개환을 통하여 합성되었다. 또한, 폴리(에틸렌 글리콜)-폴리(락틱 에시드) (MPEG-PLLA)는 촉매로서 atannous octoate를 사용하여 톨루엔에서 115 ℃에서 중합을 실시하였다. 합성된 블록 고분자는 1H-NMR, IR 그리고 GPC뿐만 아니라 수용액상에서의 온도 감응성 상전이 형상을 관찰함으로써 그 특성을 분석하였다. 소수기의 사슬길이가 증가함에 따라 솔-겔 전이 온도가 증가하였고 상전이 곡선은 낮은 농도로 급격한 기울기의 증가가 일어났다. 인체온도에서 젤 형성을 확인하기 위하여, 각각의 블록 공중합체 MPEG-PCL과 MPEG-PLLA를 수용액에 20 wt% 농도로 준비하여 쥐에 주입한 후 신체에서의 젤 형성을 확인하였다. 본 연구를 통하여 블록 공중합체가 약물과 단백질의 주사형 이식형제제 등의 생체용 재료로서 가능성을 가지고 있음을 확인하였다.

Keywords: ring-opening polymerization; sol to gel transition; biodegradable; thermosensitive; block copolymer

References
  • 1. Chen GH, Hoffman AS, Nature, 373(6509), 49 (1995)
  •  
  • 2. Yoshida R, Uchida K, Kaneko Y, Sakai K, Kikuchi A, Sakurai Y, Okano T, Nature, 374(6519), 240 (1995)
  •  
  • 3. Kwon IC, Bae YH, Kim SW, Nature, 354, 291 (1991)
  •  
  • 4. Brazel CS, Peppas NA, Macromolecules, 28(24), 8016 (1995)
  •  
  • 5. Bae YH, Okano T, Hsu R, Kim SW, Makromol. Chem. Rapid Commun., 8, 481 (1994)
  •  
  • 6. Gutowska A, Bae YH, Jacob H, Feijen J, Macromolecules, 27, 2496 (1993)
  •  
  • 7. Feil H, Bae YH, Feijen J, Kim SW, Macromolecules, 25, 5440 (1992)
  •  
  • 8. Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997)
  •  
  • 9. Bhardwaj R, Blanchard J, J. Pharm. Sci., 85, 915 (1996)
  •  
  • 10. Kim YJ, Choi S, Koh JJ, Lee M, Ko KS, Kim SW, Pharm. Res., 18, 548 (2001)
  •  
  • 11. Jeong B, Bae YH, Kim SW, J. Control. Release, 63, 155 (2000)
  •  
  • 12. Jeong B, Bae YH, Kim SW, J. Biomed. Mater. Res., 50, 171 (2000)
  •  
  • 13. Berglund F, Acta Physiol. Scand, 73, 20 (1968)
  •  
  • 14. Marcotte N, Polk A, Goosen M, J. Pharm. Sci., 79, 407 (1990)
  •  
  • 15. Yang YW, Yang Z, Zhou ZK, Attwood D, Booth C, Macromolecules, 29(2), 670 (1996)
  •  
  • 16. Malmsten M, Lindman B, Macromolecules, 25, 5446 (1992)
  •  
  • 17. Vadnere M, Amidon G, Lindenbaum S, Haslam JL, Int. J. Pharm., 22, 207 (1984)
  •  
  • 18. Jeong B, Bae YH, Kim SW, Adv. Drug Deliv. Rev., 54, 37 (2002)
  •  
  • 19. Lee WF, Chiu RJ, J. Appl. Polym. Sci., 90(8), 2214 (2003)
  •  
  • 20. Wout Z, Pec EA, Maggiore JA, Williams RH, Palicharla P, Johnston TP, J. Parenteral Sci. Technol., 46, 192 (1992)
  •  
  • 21. Palmer WK, Emeson EE, Johnston TP, Atherosclerosis, 136, 115 (1998)
  •  
  • 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. Khang G, Rhee JM, Lee JS, Lee HB, Polym. Sci. Technol., 12(1), 4 (2001)
  •  
  • 24. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  •  
  • 25. An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
  •  
  • 26. Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)
  •  
  • 27. Suh H, Jeong B, Rathi R, Kim SW, J. Biomed. Mater. Res., 42, 331 (1998)
  •  
  • 28. Leong BM, Lee DS, Shon JI, Bae YH, Kim SW, J. Polym. Sci. A: Polym. Chem., 37(6), 751 (1999)
  •  
  • 29. Jeong B, Bae YH, Kim SW, Macromolecules, 32(21), 7064 (1999)
  •  
  • 30. Choi SW, Choi SY, Jeong B, Kim SW, Lee DS, J. Polym. Sci. A: Polym. Chem., 37(13), 2207 (1999)
  •  
  • 31. Huh KM, Bae YH, Polymer, 40(22), 6147 (1999)
  •  
  • 32. Li YX, Christian V, Kissel T, J. Control. Release, 32, 121 (1994)
  •  
  • 33. Sung YK, Kim SW, Korea Polym. J., 8(5), 199 (2000)
  •  
  • 34. Bogdanov B, Vidts A, Van Den Bulcke A, Verbeeck R, Schacht E, Polymer, 39(8-9), 1631 (1998)
  •  
  • 35. Hu Y, Jiang X, Ding Y, Zhang L, Yang C, Zhang J, Chen J, Yang Y, Biomaterials, 24, 2395 (2003)
  •  
  • 36. Kim SY, Ha JC, Lee YM, J. Control. Release, 65, 345 (2000)
  •  
  • 37. Kim SY, Lee YM, Shin HJ, Kang JS, Biomaterials, 22, 2049 (2001)
  •  
  • 38. Kim SY, Lee YM, Biomaterials, 22, 1697 (2001)
  •  
  • 39. Shibasaki Y, Sanada H, Yokoi M, Sanda F, Endo T, Macromolecules, 33(12), 4316 (2000)
  •  
  • 40. Sanda F, Sanada H, Shibasaki Y, Endo T, Macromolecules, 35(3), 680 (2002)
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2024 Impact Factor : 0.6
  • Indexed in SCIE

This Article

  • 2004; 28(3): 211-217

    Published online May 25, 2004

  • Received on Dec 5, 2003
  • Accepted on Mar 24, 2004