화학공학소재연구정보센터
Macromolecular Research, Vol.11, No.5, 334-340, October, 2003
Controlled Release of Nerve Growth Factor from Sandwiched Poly(L-lactide-co-glycolide) Films for the Application in Neural Tissue Engineering
E-mail:
In order to fabricate new sustained delivery device of nerve growth factor (NGF), we developed NGFloaded biodegradable poly(L-lactide-co-glycolide) (PLGA, the mole ratio of lactide to glycolide 75:25, molecular weight: 83,000 and 43,000 g/mole, respectively) film by novel and simple sandwich solvent casting method for the possibility of the application of neural tissue engineering. PLGA was copolymerized by direct condensation reaction and the molecular weight was controlled by reaction time. Released behavior of NGF from NGF-loaded films was characterized by enzyme linked immunosorbent assay (ELISA) and degradation characteristics were observed by scanning electron microscopy (SEM) and gel permeation chromatography (GPC). The bioactivity of released NGF was identified using a rat pheochromocytoma (PC-12) cell based bioassay. The release of NGF from the NGF-loaded PLGA films was prolonged over 35 days with zero-order rate of 0.5~0.8 ng NGF/day without initial burst and could be controlled by the variations of molecular weight and NGF loading amount. After 7 days NGF released in phosphate buffered saline and PC-12 cell cultured on the NGF-loaded PLGA film for 3 days. The released NGF stimulated neurite sprouting in cultured PC-12 cells, that is to say, the remained NGF in the NGF/PLGA film at 37 ℃ for 7 days was still bioactive. This study suggested that NGF-loaded PLGA sandwich film is released the desired period in delivery system and useful neuronal growth culture as nerve contact guidance tube for the application of neural tissue engineering.
  1. Cao X, Shoichet MS, Biomaterials, 20, 329 (1999) 
  2. Mahoney MJ, Saltzman WM, J. Pharm. Sci., 85, 1276 (1996) 
  3. Rodriguez FJ, Gomez N, Perego G, Navarro X, Biomaterials, 20, 1489 (1999) 
  4. Lundberg G, Longo FM, Varon S, Brain Res., 232, 157 (1982) 
  5. Merle M, Dellon AL, Cambell JN, Chang PS, Microsurgery, 10, 130 (1989)
  6. Kerkhoff H, Jennekens FG, Clin. Neurol. Nuerosurg., 95, S103 (1993) 
  7. Tuszynski MH, Murai K, Blesch A, Grill R, Miller I, Cell Transplant, 6, 361 (1997) 
  8. Krewson CE, Karlman ML, Saltzman WM, Brain Res., 680, 196 (1995) 
  9. Jeon EK, Whang HJ, Khang G, Lee I, Rhee JM, Lee HB, Polym.(Korea), 25(6), 893 (2001)
  10. Jeon EK, Shim JY, Whang HJ, Khang G, Jo I, Lee I, Rhee JM, Lee HB, Biomater. Res., 5, 23 (2001)
  11. Hollinger JO, Schmitz JP, J. Oral Maxillofac. Surg., 45, 594 (1987)
  12. Williams DF, Mort E, J. Bioeng., 1, 231 (1997)
  13. Bostman O, J. Bone Joint Surg., 73A(1), 148 (1991)
  14. Agrawal CM, Gabriele PE, Niederauer G, Athanasiou KA, Tissue Eng., 1, 241 (1995)
  15. Cima LG, Ingber DE, Vacanti JP, Langer R, Biotechnol. Bioeng., 38, 145 (1991) 
  16. Khang G, Jeon JH, Cho JC, Lee HB, Polym.(Korea), 23(3), 471 (1999)
  17. Khang G, Jeon JH, Cho JC, Rhee JM, Lee HB, Polym.(Korea), 23(6), 861 (1999)
  18. Khang G, Lee SJ, Jeon JH, Lee JH, Lee HB, Polym.(Korea), 24(6), 869 (2000)
  19. Lee SJ, Khang G, Lee JH, Lee YM, Lee HB, Polym.(Korea), 24(6), 877 (2000)
  20. Khang G, Choi HS, Rhee JM, Yoon SC, Cho JC, Lee HB, Korea Polym. J., 8(6), 253 (2000)
  21. Khang G, Choi MK, Rhee JM, Lee SJ, Lee HB, Iwasaki Y, Nakabayashi N, Ishihara K, Korea Polym. J., 9(2), 107 (2001)
  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. Lee SJ, Khang G, Lee YM, Lee HB, J. Biomater. Sci.-Polym. Ed., 13, 197 (2002) 
  24. Khang G, Choee JH, Rhee JM, Lee HB, J. Appl. Polym. Sci., 85(6), 1253 (2002) 
  25. Iwasaki Y, Sawada S, Nakabayashi N, Khang G, Lee HB, Ishihara K, Biomaterials, 23, 3877 (2002)
  26. Choi JS, Lee SJ, Khang G, Lee I, Lee HB, Biomater. Res., 6, 17 (2002)
  27. Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Korea Polym. J., 7(2), 79 (1999)
  28. Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
  29. Cho JC, Khang G, Choi HS, Rhee JM, Lee HB, Polym.(Korea), 24(5), 728 (2000)
  30. Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002) 
  31. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  32. An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
  33. An TK, Kang HJ, Lee JS, Seong H, Jeong JK, Khang G, Hong Y, Lee HB, Polym.(Korea), 26(5), 691 (2002)
  34. Khang G, Seo SA, Choi HS, Rhee JM, Lee HB, Macromol. Res., 10(5), 246 (2002)
  35. Lee JS, Chae GS, An TK, Khang G, Cho SH, Lee HB, Macromol. Res., 11(3), 183 (2003)
  36. Lee SJ, Khang G, Lee YM, Lee HB, J. Colloid Interface Sci., 259(2), 228 (2003) 
  37. Pean JM, Venier-Julienne MC, Boury F, Menei P, Denizot B, Benoit JP, J. Control. Release, 56, 175 (1998) 
  38. Lu W, Park TG, J. Pharm. Sci. Tech., 49, 13 (1995)
  39. Cohen S, Chen LM, Apte RN, React. Polym., 25(2), 177 (1995) 
  40. Boury F, Marchais H, Proust JE, Benoit JP, J. Control. Release, 45, 75 (1997) 
  41. Khang G, Lee HB, Methods of Tissue Engineering, A. Atala and R. Lanza, Eds., Academic Press, Section II, Chap. 67, pp. 771-780 (2001)
  42. Khang G, Lee HB, Biomedical Polymers, Korean Chemical Society Press, Munundang Press, Seoul, Korea (2001)