Preparation and Characterization of O-Carboxymethyl Chitosan Ion-complexed Poly(L-Lysine) for Drug and Gene Delivery System

약물 및 유전자 전달체로 응용하기 위한 Poly(L-Lysine)이 결합된 O-Carboxymethyl Chitosan PEG의 제조와 특성

  • Nam, Joung-Pyo (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Kim, Young-Min (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Park, Jin-Su (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Lee, Eung-Jae (Department of Bioenvironmental & Chemical Engineering, Chosun College University of Science & Technology) ;
  • Choi, Chang-Yong (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Jang, Mi-Kyeong (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Nah, Jae-Woon (Department of Polymer Science and Engineering, Sunchon National University)
  • 남정표 (순천대학교 공과대학 고분자공학과) ;
  • 김영민 (순천대학교 공과대학 고분자공학과) ;
  • 박진수 (순천대학교 공과대학 고분자공학과) ;
  • 이응재 (조선이공대학 생명환경화공과) ;
  • 최창용 (순천대학교 공과대학 고분자공학과) ;
  • 장미경 (순천대학교 공과대학 고분자공학과) ;
  • 나재운 (순천대학교 공과대학 고분자공학과)
  • Received : 2010.08.13
  • Accepted : 2010.10.14
  • Published : 2010.12.10

Abstract

O-carboxymethyl water-soluble chitosan (OCMCh) prepared for enhance the application of chitosan was modified with mthoxy polyethyleneglycol (mPEG) by ion-complex for long circulation in the blood. OCMCh-PEG-PLLs was prepared by forming ion-complex with OCMCh-PEG and Poly(L-Lysine) (PLL) for drug and gene delivery system. The physicochemcal characterisitcs of OCMCh-PEG-PLLs were investigated by FT-IR, $^1H$-NMR. These results showed that CMCh-PEG-PLLs were successfully syntehsized by ion-complex. Particle size distribution and zeta potential of the OCMCh-PEG-PLLs were determined using dynamic light scattering technique. Transmission electron microscopy (TEM) was also used to observe the morphology of the OCMCh-PEG-PLLs. OCMCh-PEG-PLLs have spherical shapes with particle size 290∼390 nm. OCMCh-PEG-PLLs were showed when the feeding amount of mPEG ratio was increased, particle size and zeta potential were decreased. Based on these results, it is possible to introduction of the OCMCh-PEG-PLLs into various biomedical fields such as drug and gene delivery system.

키토산의 응용성을 높이기 위해 제조된 O-carboxymethyl water soluble chitosan (OCMCh)의 구조에 인체 내 순환시간을 증가시키기 위하여 PEG를 도입하였으며, 약물 및 유전자 전달체로 응용하기 위하여 PEG가 결합된 OCMCh-PEG를 Poly(L-Lysine) (PLL)과 이온복합체를 형성함으로써 OCMCh-PEG-PLL를 제조하였다. 제조된 OCMCh-PEG-PLL의 물리화학적특성은 적외선 분광광도계와 핵자기공명장치를 이용하여 분석하였으며, 성공적으로 PLL이 결합되었음을 확인하였다. 또한 동적광산란장치와 투과전자현미경을 통하여 PLL의 양을 고정하였을 때, PEG의 양이 증가함에 따라 입자의 크기가 감소하는 것을 볼 수 있었으며, 구형의 입자형태를 가지는 것을 확인할 수 있었다. 이상의 결과는 OCMCh-PEG-PLL이 약물 및 유전자 전달체 등과 같은 생체재료로의 응용 가능성을 가지는 것을 볼 수 있다.

Keywords

References

  1. X. Y. Wu and P. I. Lee, J. Appl. Polym. Sci., 77, 833 (2000). https://doi.org/10.1002/(SICI)1097-4628(20000725)77:4<833::AID-APP17>3.0.CO;2-4
  2. Q. Li, E. T. Dunn, E. W. Gradmaison, and M. F. A. Goosen, Journal of Bioactive and Compatible Polymers, 7, 370 (1992). https://doi.org/10.1177/088391159200700406
  3. S. Miyazaki, K. Ishii, and T. Nadai, Chem. Pharm. Bull., 29, 3067 (1981). https://doi.org/10.1248/cpb.29.3067
  4. Y. Kawashima, S. Y. Lin, Kasai, A. T. Handam, and H. Takenaka, Chem. Pharm. Bull., 33, 2107 (1985). https://doi.org/10.1248/cpb.33.2107
  5. J. Berger, M. Reist, A. Chenitem, O. F. Baeyens, J. M. Mayer, and R. Gurny, Int. J. Pharmaceutics, 288, 0378 (2004).
  6. E. R. Gariepy, M. Shive, A. Bichara, M. Berrada, D. L. Garrec, A. Chenite, and J. C. Leroux, Eur. J. Pharm. Biopharm., 57, 53 (2004). https://doi.org/10.1016/S0939-6411(03)00095-X
  7. Y. Sawayanagi, N. Nambu, and T. Naggi, Chem. Pharm. Bull., 31, 2507 (1983). https://doi.org/10.1248/cpb.31.2507
  8. J. W. Nah and M. K. Jang, J. Polym. Sci. Part A : Polym. Chem., 40, 3796 (2002). https://doi.org/10.1002/pola.10463
  9. A. P. Zhu, M. Zhang, and Z. Zhang, Polym. Int., 53, 15 (2004). https://doi.org/10.1002/pi.1275
  10. K. Y. Cai, K. D. Yao, L. I. Yang, Z. M. Yang, and X. Q. Li, J. Biomater. Sci., Polym. Ed., 12, 1303 (2001). https://doi.org/10.1163/156856202753419240
  11. J. Ragnhild, N. Hjerde, and K. M. Varum, Carbohydr. Polym., 34, 131 (1997). https://doi.org/10.1016/S0144-8617(97)00113-6
  12. J. M. Harris, New York : Plenum Press., 22, 371 (1992).
  13. J. M. Harris and S. Zalipsky, American Chemical Society, 12, 489 (1997).
  14. K. D Park and S. W. Kim, NY, Plenum Publications, 14, 283 (1992).
  15. J. H. Lee, J. Kopecek, and J. D. Andrade, J. Biomed. Mater. Res., 23, 351 (1989). https://doi.org/10.1002/jbm.820230306
  16. Y. Mori and S. Nagaoka, Trans. Am. Soc. Artif. Intern. Organs., 28, 459 (1982).
  17. N. P. Desai and A. Hubbell, J. Biomed. Mater. Res., 25, 829 (1991). https://doi.org/10.1002/jbm.820250704
  18. S. Jeon and J. Andrade, J. Colloid Interface Sci., 142, 159 (1991). https://doi.org/10.1016/0021-9797(91)90044-9
  19. NEKTAR therapeutics Co, Catalogue Nektar Advance PEGylation (2005-2006).
  20. F. M. Veronese and J. M. Harris, Adv. Drug Deliv. Rev., 54, 453 (2002). https://doi.org/10.1016/S0169-409X(02)00020-0
  21. F. M. Veronese, C. Monfardin, P. Caliceti, O. Schiavon, M. D. Scrawen, and D. Beer, J. Control. Rel., 40, 199 (1996). https://doi.org/10.1016/0168-3659(95)00185-9
  22. 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
  23. M. Sela and E. Katchalski, Adv. Protein Chem., 14, 391 (1959). https://doi.org/10.1016/S0065-3233(08)60614-2
  24. J. P. Nam, D. G. Kim, Y. B. Kim, Y. I. Jeong, M. K. Jang, and J. W. Nah, J. Chitin Chitosan., 13, 105 (2008).
  25. J. P. Nam, J. K. Park, C. Y. Choi, Y. K. Park, M. K. Jang, and J. W. Nah, J. Chitin Chitosan., 15, 12 (2010).