화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.28, No.4, 335-343, July, 2004
Export Citation
글리콜라이드 단량체를 함유한 BICNU 함유 다중층 PLGA 웨이퍼의 제조 및 특성결정
Preparation and Characterization of BICNU-loaded Multi-Layer PLGA Wafer Containing Glycolide Monomer
채강수, 이진수, 정제교1, 조선행2, 이해방2, 강길선†
  • 전북대학교 유기신물질공학과
  • 1삼천당제약 중앙연구소
  • 2한국화학연구원 나노생체재료고분자팀
Gang Soo Chae, Jin Soo Lee, Je Kyo Jeong1, Sun Hang Cho2, Hai Bang Lee2, and Gilson Khang†
  • Department of Advanced Organic Materials Engineering, Chonbuk national University, 664-14, Dukjin Ku, Jeonju 561-756, Korea
  • 1Research Center, Samchundang Pharm. Co. Ltd., P.O. Box 289, Youngdeungpo, Seoul, 150-037, Korea
  • 2Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejon 305-506, Korea
E-mail:
초록
카뮤스틴 (1,3-bis(2-chloroethyl)-1-nitrosourea, BICNU)은 뇌종양 치료를 위하여 임상적으로 사용되는 약물로 짧은 생물학적 반감기를 가지고 있어 장기방출에 적합하지 않다. 하지만, poly(D,L-lactide-co-glycolide)(PLGA)는 벌크 분해 특성으로 인해 약물의 장기방출에 유용하며, PLGA의 유도체인 글리콜라이드 단량체는 독성이 없고 PLGA와 유사한 생분해성을 가지고 있어 BICNU의 방출조절에 이용된다. 이 실험에서 BICNU를 함유한 PLGA 웨이퍼는 일반적인 직접압축법에 의해 제조한 후 BICNU의 방출거동과 웨이퍼의 분해속도를 전자주사현미경, 핵자기공명장치 그리고 젤투과크로마토그래피를 통해 관찰하였다. 또한, 글리콜라이드 단량체의 함량변화에 따른 다중층 웨이퍼를 제조하여 단일층 웨이퍼와의 방출거동을 비교하였다. 이러한 결과들로부터 BICNU를 함유한 PLGA 웨이퍼의 약물방출은 BICNU와 글리콜라이드 단량체의 함량이 증가할수록 증가하였고, 다중층 웨이퍼에서 외부층의 글리콜라이드 단량체와 BICNU가 약물방출 거동과 분해속도에 영향을 미친다는 것을 확인하였다.
Carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BICNU) used as antineoplastic drug for the treatment of brain tumor is not appropriate for the long term delivery, because it has short biological half life. Therefore, poly(D,L-lactide-co-glycolide) (PLGA) is useful as drug carrier for the long term delivery due to bulk erosion property. Glycolide monomer is applied to release of BICNU owing to non-toxic and monomeric components after biodegradation of PLGA. In this study, BICNU-loaded PLGA wafers with or without glycolide monomer were fabricated by conventional direct compression method for the sustained release of BICNU. These wafers were observed for their release profiles of BICNU and degradation rates by SEM, NMR, and GPC. Furthermore, we make multi-layer wafers and compare them with release profiles of conventional wafer. From these results, drug release of BICNU-loaded PLGA wafers was increased with increasing the glycolid monomer contents. We confirmed that glycolide monomer and BICNU contents in barrier-layer influenced the drug release profiles and degradation rate.
Keywords:BICNU;PLGA wafer;glycolide monomer;zero-order profile
  1. Wang C, Li J, Teo CS, Lee T, J. Control. Release, 61, 21 (1999) 
  2. An TK, Kang HJ, Lee JS, Seong H, Jeong JK, Khang G, Hong Y, Lee HB, Polym.(Korea), 26(5), 691 (2002)
  3. Moon DS, Khang G, Seong HS, Rhee JM, Lee JS, Lee HB, Biomater. Res., 4, 107 (2000)
  4. Khang G, Rhee JM, Lee JS, Lee HB, Polym. Sci. Technol., 12(1), 4 (2001)
  5. Seong HS, Moon DS, Khang G, Lee HB, Macromol. Chem. Symp., 14, 95 (2001)
  6. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  7. Miyajima M, Koshika A, Okada J, Kusai A, Ikida M, Int. J. Pharm., 169, 255 (1998) 
  8. den Jartigh J, Langebrook R, Vermeji P, J. Pharm. Biomed. Anal., 11, 977 (1993) 
  9. Mautalen CA, Casco CA, Gonzalez D, Ghiringhelli GR, Massironi C, Br. Med. J., 288 (1984)
  10. Fitton A, McTavish D, Drugs, 41, 289 (1991)
  11. Khang G, Rhee JM, Lee JS, Lee HB, Polym. Sci. Technol., 12(1), 4 (2001)
  12. Khang G, Lee HB, Biomedical Polymers, Korean Chemical Society Press, Munundang, Seoul (2001)
  13. Choi HS, Kim SW, Yun DI, Khang G, Rhee JM, Kim YS, Lee HB, Polym.(Korea), 25(3), 334 (2001)
  14. Seong HS, Moon DS, Khang G, Lee HB, Macromol. Chem. Symp., 4, 95 (2001)
  15. Seo SA, Choi HS, Lee DH, Khang G, Lee HB, Polym.(Korea), 25(6), 884 (2001)
  16. Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002) 
  17. Walter KA, Tarmargo RJ, Olivi A, Burger PC, Brem H, Neurosurgery, 37, 1129 (1995)
  18. Lee L, Treatise on Controlled Drug Delivery, Marcel Dekker Inc., New York (1992)
  19. Hildgen P, Mcmullen JN, J. Control. Release, 34, 263 (1995) 
  20. Danckwerts MP, Int. J. Pharm., 112, 34 (1994)
  21. Kim C, Pharm. Res., 12, 1045 (1995) 
  22. Benkorah AY, McMullen JN, J. Control. Release, 32, 155 (1994) 
  23. Conte U, Maggi L, Colombo P, Manna AL, J. Control. Release, 26, 39 (1993) 
  24. Scott DC, Hollenbeck RG, Pharm. Res., 8, 156 (1991) 
  25. Brooke D, Washkuhn RJ, J. Pharm. Sci., 66, 159 (1977) 
  26. Lipper RA, Higuchi WI, J. Pharm. Sci., 66, 163 (1977) 
  27. Lin WJ, Lee HG, J. Control. Release, 89, 179 (2003) 
  28. Hildgen P, McMullen JN, J. Control. Release, 34, 263 (1995) 
  29. Conte U, Maggi L, Biomaterials, 17, 889 (1996) 
  30. Narasimhan B, Langer R, J. Control. Release, 47, 13 (1997) 
  31. Streubel A, Siepmann J, Peppas NA, Bodmeier R, J. Control. Release, 69, 455 (2000) 
  32. Fredrikson K, Lundgren P, Acta Pharm. Scand., 23, 115 (1986)