공업화학 (Applied Chemistry for Engineering)

  • 제21권6호
  • /
  • Pages.593-602
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  • 2010
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  • 1225-0112(pISSN)
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  • 2288-4505(eISSN)
한국공업화학회 (The Korean Society of Industrial and Engineering Chemistry)
권호 표지

생체 내 특정 조직의 표적을 위한 키토산 유도체

Chitosan Derivatives for Target of Specific Tissue in the Body

  • 장미경 (순천대학교 공과대학 고분자공학과) ;
  • 나재운 (순천대학교 공과대학 고분자공학과)
  • Jang, Mi-Kyeong (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Nah, Jae-Woon (Department of Polymer Science and Engineering, Sunchon National University)
  • 투고 : 2010.10.04
  • 발행 : 2010.12.10
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⟨ 이전 논문 다음 논문 ⟩

초록

천연고분자물질로서 키토산(chitosan)은 생체적합성, 생분해성, 무독성과 같은 생체재료로서의 우수한 물리화학적 특성에도 불구하고 산(acid)으로 용해하여야 한다는 문제점으로 인해 유전질병이나 암과 같은 불치병의 치료를 위한 생리활성 물질의 생체 내 전달물질로서의 응용이 어려운 실정이다. 따라서 키토산의 이러한 문제점을 획기적으로 해결한 높은 반응성과 강한 양전하(+)를 띠고 있는 저분자량 수용성 키토산(low molecular weight water-soluble chitosan, LMWSC)을 이용하여 난용성 약물뿐만 아니라 치료유전자와 같은 생리활성물질을 안전하게 생체 내 표적위치에 운반할 수 있는 전달체를 제조할 수 있고, 인체 내 무해하고 치료효율이 높은 치료시스템을 개발할 수 있을 것으로 사료된다. 또한 질병의 치료를 위해 무엇보다 중요한 인자는 특정 병소조직에만 발현되는 항원이나 수용체를 밝혀내고 이들과 결합할 수 있는 항체나 리간드를 다양한 생체재료에 개질함으로써 질병 치료의 효율을 높이는 것이 가장 중요한 전략이라고 할 수 있다. 약물이나 유전자를 전달할 수 있는 많은 양이온성 합성고분자에 대한 연구가 활발히 이루어지고 있으나 체내 독성이나 효율성 면에서 많은 문제점을 가지고 있다. 따라서 본 총설에서는 인체 내 전달 효율을 높이기 위한 기능성기의 도입과 유전자와의 복합체 형성을 가능하게 하는 유리 아민기를 가진 인체 무해한 저분자량 수용성 키토산을 이용하여 특정 조직을 표적할 수 있는 다양한 기능성기 도입의 특성과 치료 전략에 대해 기술하고자 한다. 이러한 전달체의 개발은 앞으로 인간에게 유발되는 가장 난치병 중의 하나인 암 치료에 있어 밝은 전망이 될 수 있을 것으로 사료된다.

Chitosan as a natural polymer has superior physicochemical properties such as biocompatibility, biodegradability and nontoxicity, but application of chitosan for therapy of cancer and gene related-disease has been limited by poor solubility in aqueous solution. Therefore, low molecular weight water-soluble chitosan (LMWSC) with high reactivity and strong positive charge can be applied as a delivery system having function to carry in the specific tissue the bioactive material like poor solubility drug, or therapeutic gene and developed as a therapeutic system having good therapeutic efficiency. The most important factor for therapy of various diseases is to reveal the antigen or receptor expressed in specific lesion tissue and the antibody and ligand which can bind with antigen is to introduce at the biomaterials for enhancement the therapeutic efficiency. The studies for cationic synthetic polymer as drug or gene delivery have been actively performed, but it has many problems such as toxicity in the body, therapeutic efficiency. From this point of view, this article demonstrated the introduction of functional groups to target the specific tissue and therapeutic strategy using the modification of LMWSC with free-amine group. The development of these delivery system will provide a positive vision for cancer therapy.

키워드

참고문헌

  1. A. C. Antony, Annu Rev Nutr., 15, 1332 (1996).
  2. R. J. Lee and P. S. Low, J. Biol Chem., 4, 3198 (1994).
  3. S. Mansouri, Y. Cuie, F. Winnik, Q. Shi, P. Lavigne, M. Benderdour, E. Beaumont, and J. C. Fernandes, Biomaterials, 27, 2060 (2006). https://doi.org/10.1016/j.biomaterials.2005.09.020
  4. H. Wang P. Zhao, X. Liang, X. Gong, T. Song, R. Niu, and J. Chang, Biomaterials, 31, 4129 (2010). https://doi.org/10.1016/j.biomaterials.2010.01.089
  5. B. Stella, S. Arpicco, M. T. Peracchia, D. Desmaele, J. Hoebeke, M. Renoir, J. D'Angelo, L. Cattel, and P. Couvreur, J. Pharm. Sci., 89, 1452 (2000). https://doi.org/10.1002/1520-6017(200011)89:11<1452::AID-JPS8>3.0.CO;2-P
  6. R. E. Eliaz and F. C. Szoka, Cancer Research, 61, 2592 (2001).
  7. S. X. Song, D. Liu, J. L. Peng, H. W. Deng, Y. Guo, and L. X. Xu, FASEB J, 23, 1396 (2009). https://doi.org/10.1096/fj.08-117002
  8. K. W. Leong, H. Q. Mao, V. L. Truong-Le, K. Roy, S. M. Walsh, and J. T. August, J. Control. Release, 53, 183 (1998). https://doi.org/10.1016/S0168-3659(97)00252-6
  9. I. V. Zhigaltsev, N. Aurer, Q. F. Leone, E. Len, and J. Wang, J. Control. Release, 104, 103 (2005). https://doi.org/10.1016/j.jconrel.2005.01.010
  10. C. Berkland, M. King, A. Cox, K. Kim, and D. W. Pack, J. Control. Release, 82, 137 (2002). https://doi.org/10.1016/S0168-3659(02)00136-0
  11. F. L. Mi, T. B. Wong, S. S. Shyu, and S. F. Chang, J. Appl. Polym. Sci., 71, 747 (1999). https://doi.org/10.1002/(SICI)1097-4628(19990131)71:5<747::AID-APP9>3.0.CO;2-6
  12. G. Gregoriadis, Trends Biotechnol., 13, 527 (1995). https://doi.org/10.1016/S0167-7799(00)89017-4
  13. R. Hejazi and M. Amiji, J. Conttol. Release, 89, 151 (2003). https://doi.org/10.1016/S0168-3659(03)00126-3
  14. J. W. Nah and M. K. Jang, J. Polym. Sci. Part A: Polym. Chem., 40, 3796 (2002). https://doi.org/10.1002/pola.10463
  15. M. Thanou, J. C. Verhoef, and H. E. Junginger, Adv. Drug Delivery Rev., 52, 117 (2001). https://doi.org/10.1016/S0169-409X(01)00231-9
  16. K. Ogawa, T. Yui, and K. Okuyama, International Journal of Biological Macromolecules, 34, 1 (2004). https://doi.org/10.1016/j.ijbiomac.2003.11.002
  17. M. A. Wolfert, P. R. Dash, O. Nazarova, D. Oupicky, L. W. Seymour, S. Smart, J. Strohalm, and K. Ulbrich, Bioconfug. Chem, 10, 993 (1999). https://doi.org/10.1021/bc990025r
  18. M. K. Jang and J. W. Nah, Bull. Korean Chem. Sci., 24, 1303 (2003). https://doi.org/10.5012/bkcs.2003.24.9.1303
  19. W. G. Liu and K. D. Yao, J. Control. Release, 83, 1 (2002). https://doi.org/10.1016/S0168-3659(02)00144-X
  20. D. G. Kim, Y. I. Jeong, and J. W. Nah, J. Appl. Polym. Sci., 105, 3246 (2007). https://doi.org/10.1002/app.26480
  21. T. Ouchi, H. Nishizawa, and Y. Ohya, Polymer, 39, 5171 (1998). https://doi.org/10.1016/S0032-3861(97)10020-9
  22. Y. I. Jeong, D. G. Kim, M. K. Jang, and J. W. Nah, Carbohydrate Research, 343, 282 (2008). https://doi.org/10.1016/j.carres.2007.10.025
  23. N. V. Majeti, and K. Ravi, Reactive & Functional Polymers, 46, 1 (2000). https://doi.org/10.1016/S1381-5148(00)00038-9
  24. O. Skaugrud, Manufacturing Chemist, 60, 31 (1989).
  25. Y. H. Bae, T. Okano, and S. W. Kim, J. Polym. Sci. Polym. Phys., 28, 923 (1990). https://doi.org/10.1002/polb.1990.090280609
  26. K. Dusek and G. Responsive, Advances in Polymers Science. Springer verlag, 109 (1993).
  27. R. Yoshida, K. Sakai, T. Okano, Y. Sakurai, Y. H. Bae, and S. W. Kim, J. Biomater. Sci. Plymer Edn., 3, 155 (1991).
  28. H. Wei, X. Z. Zhang, W. Q. Chen, S. X. Cheng, and R. X. Zhuo, J. Bio. Mater. Res. Part A, 83A, 980 (2006).
  29. Y. Cao, C. Xhang, W. Shen, X. Cheng, L. L. Yu, and Q. Ping, J. Control. Release, 120, 186 (2007). https://doi.org/10.1016/j.jconrel.2007.05.009
  30. N. Ozdemir, A. Tuncel, M. Kang, and E. B. Denkbas, J. Nanosci. Naotechnol., 6, 2804 (2006). https://doi.org/10.1166/jnn.2006.463
  31. H. Feil, Y. H. Bae, J. Feijen, and S. W. Kim, Macromolecules, 25, 5528 (1992). https://doi.org/10.1021/ma00046a063
  32. M. Casolaro, Polymer, 38, 4215 (1997). https://doi.org/10.1016/S0032-3861(96)01010-5
  33. H. Feil, Y. H. Bae, J. Feijen, and S. W. Kim, Macromolecules, 26, 2496 (1993). https://doi.org/10.1021/ma00062a016
  34. M. Kurisawa, M. Yokoyama, and T. Okano, J. Control. Release, 69, 127 (2000). https://doi.org/10.1016/S0168-3659(00)00297-2
  35. H. S. Jang, C. Choi, D. G. Kim, M. K. Jang, and J. W. Nah, J. Chitin Chitosan, 12, 213 (2007).
  36. A. P. Zhu, M. Zhang, and Z. Zhang, Polym. Int., 53, 15 (2004). https://doi.org/10.1002/pi.1275
  37. K. Y. Cai, K. D. Yao, L. Yang, and X. Q. Li, J. Biomater. Sci., Polym., 12, 1303 (2001). https://doi.org/10.1163/156856202753419240
  38. H. Zheng and Y. M. Du, Polym. Mater. Sci. Eng., 18, 124 (2002).
  39. J. P. Nam, D. G. Kim, Y. I. Jeong, M. K. Jang, and J. W. Nah, J. Chitin Chitosan, 12, 151 (2007).
  40. M. K. Jang and J. W. Nah, Colloid and Surface B : Biointerfaces, in press.
  41. M. K. Jang and J. W. Nah, Chitin, Chitosan, Oligosaccharides and Their Derivatives, CRC Press, 2010, Chapter 24.
  42. C. Choi, D. G. Kim, M. J. Jang, T. H. M. K. Jang, and J. W. Nah, J. Appl. Polym Sci., 102, 3545 (2006). https://doi.org/10.1002/app.24809
  43. B. Agellon and E. C. Torchia, Biochim. Biophy., 198, 1386 (2000).
  44. K. Y. Lee, W. H. Jeong, I. C. Kwon, Y. Kim, and S. Y. Jeong, Macromolecules, 31, 378 (1998). https://doi.org/10.1021/ma9711304
  45. S. Y. Chae, S. Son, M. Lee, M. K. Jang, and J. W. Nah, J. Control. Release, 109, 330 (2005). https://doi.org/10.1016/j.jconrel.2005.09.040
  46. J. H. Senior, K. R. Trimble, and R. Maskiewicz, Biochem., Biophys., Acta, 1070, 173 (1991). https://doi.org/10.1016/0005-2736(91)90160-A
  47. H. M. Temin, Hum. Gene Ther., 1, 111 (1990). https://doi.org/10.1089/hum.1990.1.2-111
  48. V. S. Trubetskoy, V. P. Torchilin, S. J. Kennel, and L. Huang, Bioconjugate Chem., 3, 323 (1992). https://doi.org/10.1021/bc00016a011
  49. Y. H. Choi, F. Liu, J. S. Kim, Y. K. Choi, J. S. Park, and S. W. Kim, J. Control. Release, 54, 39 (1998). https://doi.org/10.1016/S0168-3659(97)00174-0
  50. J. W. Nah, L. Yu, S. Han, C. Ahn, and S. W. Kim, J. Control. Release, 78, 273 (2002). https://doi.org/10.1016/S0168-3659(01)00499-0
  51. C. Song, V. Labhasetwar, X. Cui, T. Underwood, and R. J. Levy, J. Control, Release, 54, 201 (1998). https://doi.org/10.1016/S0168-3659(98)00016-9
  52. J. F. Mitchel, D. B. Fram, D. Palme, R. Foster, J. A. Hirst, M. A. Azrin, L. M. Bow, A. M. Eldin, D. D. Waters, and R. G. Mckay, Circulation, 91, 785 (1995). https://doi.org/10.1161/01.CIR.91.3.785
  53. D. Voet and J. G. Voet, Biochemistry, ed. J. Stiefel, 1. 305, Wiley, New York (1990).
  54. D. Voet and J. G. Voet, Biochemistry, ed. J. Stiefel, 1. 309, Wiley, New York (1990).
  55. R. J. Havel, Atherosclerosis, 141 Suppl 1, S1 (1998). https://doi.org/10.1016/S0021-9150(98)00211-1
  56. M. Lougheed, E. D. Moore, D. R. Scriven, and U. P. Steinbrecher, Arterioscler Thromb Vasc Biol., 19, 1881 (1999). https://doi.org/10.1161/01.ATV.19.8.1881
  57. C. Choi, M. K. Jana, and J. W Nah, Polymer (Korea), 30, 279 (2006).
  58. P. Carmeliet and R. K. Jain. Nature, 407, 249 (2000). https://doi.org/10.1038/35025220
  59. P. Carmeliet and R. K. Jain, Nature, 407, 249 (2000). https://doi.org/10.1038/35025220
  60. K. A. Thomas, J. Biol. Chem, 271, 603 (1996). https://doi.org/10.1074/jbc.271.2.603
  61. W. J. Kim, J. W. Yockman, J. H. Jeong, L. V. Christensen, M. Lee, Y. H. Kim, and S. W. Kim, J. Control. Release, 114, 381 (2006). https://doi.org/10.1016/j.jconrel.2006.05.029
  62. A. Akinc, M. Thomas, A. M. Klibanov, and R. Langer, J. Gene Med., 7, 657 (2005).
  63. A. Kichler, C. Leborgne, E. Coeytaux, and O. Danos, J. Gene Med., 3, 135 (2001). https://doi.org/10.1002/jgm.173
  64. J. K. Park, D. G. Kim, C. Choi, M. K. Jang, and J. W. Nah, J. Korean Ind. Eng. Chem, 6, 607 (2007).