폴리머 (Polymer(Korea))

  • 제29권3호
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  • Pages.277-281
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  • 2005
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  • 0379-153X(pISSN)
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  • 2234-8077(eISSN)
한국고분자학회 (The Polymer Society of Korea)
권호 표지

폴리에틸렌이민으로 수식된 양이온 리포좀의 제조 및 유전자 전달체로서의 응용

Preparation of Cationic Liposomes Modified by Polyethylenimine and Their Application as Gene Carrier

  • 서동환 (한국화학연구원 화학소재부) ;
  • 신병철 (한국화학연구원 화학소재부) ;
  • 김문석 (한국화학연구원 화학소재부)
  • Seo, Dong-Hoan (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Shin, Byung-Cheol (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Kim, Moon-Suk (Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology)
  • 발행 : 2005.05.01
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⟨ 이전 논문 다음 논문 ⟩

초록

비바이러스성 DNA 전달체 중에서 최근 양이온성 고분자와 양이온성 리피드들은 많이 연구되어 왔다. 본 연구에서는 비바이러스성 유전자 전달체로서 양이온성 고분자인 폴리에틸렌이민(PEI)을 리피드에 수식하여 더 효과적인 전달체를 제조하고자 하였다. 새로운 양이온성 리피드(PEI-DSPE)는 1,2-디아실-sn-글리세로-3-포스포에탄올아민(DSPE)과 PEI를 이용하여 고수율로 합성하였다. 1,2-디스테아로일-sn-글리세로-3-포스포콜린(DSPC), L-$\alpha$-포스파티딜콜린(소이-하디드로제네티드) (HSPC), 콜레스테롤(CHOL) 및 합성된 PEI-DSPE를 이용하여 리포좀을 제조하였다. 리포좀 제조는 리피드 함량에 대해 양이온성이 도입된 PEI-DSPE의 양을 증가시키며 수행하였다. 제조된 리포좀의 크기는 PEI-DSPE의 첨가량이 증가할수록 감소하였으며 리포좀의 표면전하 또한 양의 값으로 증가됨을 관찰할 수 있었다. PEI-DSPE 양적 변화에 따라 제조된 리포좀을 이용하여 DNA의 복합체 형성에 관한 결과 사용된 리포좀의 함량이 증가할수록 DNA와의 복합체 형성이 용이함을 전기영동 및 형광 측정을 통해 관찰할 수 있었으며 형성된 복합체가 사용된 리포좀 함량이 증가할수록 양이온적 성질이 증대됨을 관찰할 수 있었다. 그러므로 본 연구에서 합성한 PEI-DSPE를 사용하여 제조된 리포좀이 유전자 전달체로서의 가능성을 갖고 있음을 확인할 수 있었다.

Recently, various curriers prepared by the modification both cationic polymers and liposomes have been examined. In this work, we prepared the lipid with polyethylenimine (PEI) to investigate the possibility as effective DNA carrier. Cationic lipid (PEI-DSPE) was synthesized by the reaction of PEI and 1,2-diacyl-sn-glycero-3-phosphoetha-nolamine (DSPE). The liposomes were prepared by the concenoation changes of PEI-DSPE for a mixture of 1,2-disteanyl-sn-glycero-3-phosphocholine (DSPC), L-$\alpha$-phosphatidylcholine, hydrogenated (HSPC) and cholesterol (CHOL). Particle size decreased as PEI-DSPE concentration increased. In addition, the charge of liposome surface increased to positive value according to increasing the relative of PEI-DSPE concentration. The complexation of DNA was confirmed by gel retardation assay and fluorescence measurement. The surface charge of liposome/DNA complexes increased as the liposome concentration or surface charge of liposome increased. In conclusion, we confirmed that the prepared liposomes have the possibility as a DNA carrier.

키워드

참고문헌

  1. A. E. Aneed, Eur. J. Pharmacol, 498, 1 (2004) https://doi.org/10.1016/j.ejphar.2004.06.054
  2. P. M. Kraan, F. A. J. Loo, and W. B. Berg, Biomaterials, 25, 1497 (2004) https://doi.org/10.1016/S0142-9612(03)00493-9
  3. C. Chastel, J. Jiricny, and R. Jaussi, DNA Repair, 3, 201 (2004) https://doi.org/10.1016/j.dnarep.2003.12.002
  4. P. R. Lowenstein and M. G Castro, Curr. Opin. Pharmacol., 4, 91 (2004) https://doi.org/10.1016/j.coph.2003.09.009
  5. H. M. Kankkonen, M. P. Turunen, M. O. Hiltunen, P. Lehtolainen, J. Koponen, P. Leppanen, A. M. Turunen, and S. Y. Herttuala, J. Mol. Cell. Cardiol., 36, 333 (2004) https://doi.org/10.1016/j.yjmcc.2003.11.011
  6. C. M. Liu, D. P. Liu, W. J. Dong, and C. C. Liang, Biochem. Bioph. Res. Comm., 313, 716 (2004) https://doi.org/10.1016/j.bbrc.2003.11.174
  7. L. Xing and S. K. Tikoo, Virology, 321, 372 (2004) https://doi.org/10.1016/j.virol.2003.12.025
  8. R. Meulenbroke, K. Sargent, J. Lunde, B. Jasmin, and R. Parks, Mol. Ther., 9, 617 (2004) https://doi.org/10.1016/j.ymthe.2004.01.012
  9. M. A. F. V. Goncalves, I. Velde, K. S. Shoshan, D. Valerio, and A. A. F. Vries, Virology, 321, 287 (2004) https://doi.org/10.1016/j.virol.2004.01.007
  10. D. Boden, O. Pusch, F. Lee, L. Tucker, and B. Ramratnam, Mol. Ther., 9, 396 (2004)
  11. D. Lesage, A. Cao, D. Briane, N. Lievre, R. Coudert, M. Raphael, J. L. Salzmann, and E. Taillandier, Biochi. Bio. Acta, 1564, 393 (2004) https://doi.org/10.1016/S0005-2736(02)00474-1
  12. A. Kim, E. H. Lee, S. H. Choi, and C. K. Kim, Biomaterials, 25, 305 (2004) https://doi.org/10.1016/S0142-9612(03)00534-9
  13. M. Singh and M. Ariatti, J. Control. Release, 92, 383 (2003) https://doi.org/10.1016/S0168-3659(03)00360-2
  14. X. Liu, D. Erickson, D. Li, and U. J. Krull, Analy. Chim. Acta, 507, 55 (2004) https://doi.org/10.1016/j.aca.2003.10.075
  15. T. Segura, M. J. Volk, and L. D. Shea, J. Control. Release, 93, 69 (2003) https://doi.org/10.1016/j.jconrel.2003.08.003
  16. J. H. Steven Kuo, Y. L. Lo, M. D. Shau, and J. Y. Cherng, J. Control. Release, 81, 321 (2002) https://doi.org/10.1016/S0168-3659(02)00079-2
  17. C. R. Dass, Int. J. Pharma., 267, 1 (2003) https://doi.org/10.1016/j.ijpharm.2003.08.010
  18. S. J. Sung, S. H. Min, K. Y. Cho, S. N. Lee, Y. J. Min, Y. I. Yeom, and J. K. Park, Biol. Pharm, Bull., 26, 492 (2003) https://doi.org/10.1248/bpb.26.492
  19. J. H. Chio, J. S. Chio, H. Suh, and J. S. Park, Bull. Korean Chem. Soc., 22, 46 (2001)
  20. K. Sagara and S. W. Kim, J. Control. Release, 79, 271 (2002) https://doi.org/10.1016/S0168-3659(01)00555-7
  21. Y. Lu and P. S. Low, Adv. Drug Deliver. Rev., 54, 675 (2002) https://doi.org/10.1016/S0169-409X(02)00042-X
  22. C. H. Ahn, S. Y. Chae, Y. H. Bae, and S. W. Kim, J. Control. Release, 80, 273 (2002) https://doi.org/10.1016/S0168-3659(01)00547-8
  23. W. T. Godbey, M. A. Barry, P. Saggau, K. K. Wu, and A. G. Mikos, J. Biomed. Mater. Res., 51, 321 (2000) https://doi.org/10.1002/1097-4636(20000905)51:3<321::AID-JBM5>3.0.CO;2-R
  24. W. T. Godbey, K. K. Wu, and A. G. Mikos, J. Control. Release, 60,149 (1999) https://doi.org/10.1016/S0168-3659(99)00090-5
  25. W. T. Godbey, K. K. Wu, and A. G. Mikos, J. Biomed. Mater. Res., 45, 268 (1999) https://doi.org/10.1002/(SICI)1097-4636(19990605)45:3<268::AID-JBM15>3.0.CO;2-Q
  26. D. Fischer, T. Bieber, Y. Li, H. P. Elsasser, and T. Kissel, Pharmaceut. Res., 16, 1273 (1999) https://doi.org/10.1023/A:1014861900478
  27. D. H. Sea, S. H. Kim, G. Khang, S. C. Chi, B. C. Shin, and M. S. Kim, Polymer(Korea), 29, 135 (2005)
  28. W. Guo, M. A. Gosselin, and R. J. Lee, J. Control. Release, 83, 121 (2002) https://doi.org/10.1016/S0168-3659(02)00167-0
  29. C. H. Lee, Y. H. Ni, C. C. Chen, C. K. Chou, and F. H. Chang, Biochi. Bio. Acta, 1611, 55 (2003) https://doi.org/10.1016/S0005-2736(03)00027-0
  30. N. Oku, Y. Yamazaki, M. Matsuura, M. Sugiyama, M. Hasegawa, and M. Nango, Adv. Drug Deliver. Rev., 52, 209 (2001) https://doi.org/10.1016/S0169-409X(01)00199-5
  31. M. Matsuura, Y. Yamazaki, M. Sugiyama, M. Kondo, H. Ori, M. Nango, and N. Oku, Biochi. Bio. Acta, 1612, 136 (2003) https://doi.org/10.1016/S0005-2736(03)00109-3
  32. M. Sugiyama, M. Matsuura, Y. Takeuchi, J. Kosaka, M. Nango, and N. Oku, Biochi. Bio. Acta, 1660, 24 (2004) https://doi.org/10.1016/j.bbamem.2003.10.012
  33. Y. Yamazaki, M. Nango, M. Matsuura, Y. Hasegawa, M. Hasegawa, and N. Oku, Gene therapy, 7, 1148 (2000) https://doi.org/10.1038/sj.gt.3301217
  34. Y. J. Park, D. E. Nam, D. H. Seo, H. D. Han, T. W. Kim, M. S. Kim, and B. C. Shin, Polymer(Korea), 28, 502 (2004)
  35. J. D. Castile and K. M. G. Taylor, Int. J. Pharma., 221, 197 (2001) https://doi.org/10.1016/S0378-5173(01)00691-3
  36. V. P. Torchilin, T. S. Levchenko, K. R. Whiteman, A. A. Yaroslavov, A. M. Tsatsakis, A. K. Rizos, E. V. Michailova, and M. I. Shtilman, Biomaterials, 22, 3035 (2001) https://doi.org/10.1016/S0142-9612(00)00074-0
  37. K. K. Son, D. H. Patel, D. Tkach, and A. Park, Biochi. Bio. Acta, 1466, 11 (2000) https://doi.org/10.1016/S0005-2736(00)00176-0