pH-Sensitive Release of Indomethacin from Curdlan Acetate Microspheres

Curdlan Acetate Microspheres를 이용한 Indomethacin의 pH 민감성 방출

  • Lee Chang-Moon (Interdisciplinary Program of Biomedical Engineering, Chonnam National University) ;
  • Lee Young-Jin (Department of Material Chemical and Biochemical Engineering, Chonnam National University) ;
  • Kim Hyung-Ju (Interdisciplinary Program of Biomedical Engineering, Chonnam National University) ;
  • Park Hee-Jung (Department of Material Chemical and Biochemical Engineering, Chonnam National University) ;
  • Lee Ki-Young (Faculty of Applied Chemical Engineering & The Research Institute for Catalysis, Chonnam National University)
  • 이창문 (전남대학교 의공학협동과정) ;
  • 이영진 (전남대학교 물질생물화학공학과) ;
  • 김형주 (전남대학교 의공학협동과정) ;
  • 박희정 (전남대학교 물질생물화학공학과) ;
  • 이기영 (전남대학교 응용화학공학부 및 촉매연구소)
  • Published : 2005.02.01

Abstract

Curdlan, a natural $\beta-1,3-glucan,$ has been studied as drug carrier due to its unique properties including its thermal gelling characters. In this study, curdlan was chemically acetylated for pH-sensitive drug delivery. Curdlan acetate microspheres(CAMs) were prepared by the solvent evaporation method. The size of the CAMs was below $200{\mu}m.$ The drug loading efficiency of microspheres was approximately $58.44\%$. In the swelling test, the CAMs showed pH-sensitive behavior. The swelling capacity of microspheres at pH 7.4 was much greater than at pH 1.4. Also, release rate of indomethacin(IND) at pH 7.4 from the CAMs was faster than that at pH 1.4. Therefore the CAMs have potential for the controlled release of IND over an extended period of time.

생분해성인 curdlan을 아세틸화하여 소수성 약물인 IND의 치료효과를 증진시킬 수 있는 약물전달시스템 개발을 위한 실험을 수행한 결과, IND가 포함된 CAMs를 제조할 수 있었고, IND의 loading efficiency는 $58.44\%$였다. 약물 방출 거동에 영향을 미치는 요인 중 제조한 CAMs의 swelling 특성은 처음 1시간 동안 pH 1.4에서는 아무런 변화가 없었고 PH 7.4에서는 $30\%$의 swelling을 보였고 pH 1.4에서보다 pH 7.4에서의 swelling이 약 3배 높았다. 또한 CAMs로부터 IND의 방출은 pH 1.4에서보다 pH 7.4에서 약 15배 이상 증가하였다. 이러한 결과로 CAMs는 IND의 약물전달시스템으로 유용할 것이며 특히 pH에 의존하는 약물방출 경향을 보였다.

Keywords

References

  1. Kwon, I. C., K. Kim, S. Kim, H. Chung, and S. Y. Jeong (2004), Drug delivery system using chitosan nanoparticles, Polym. Sci. Technol. 15, 396-401
  2. Shin, B. C., S. H. Cho, and M. S. Kim (2003), Nanoparticles for drug delivery, Polym. Sci. Technol. 14, 298-307
  3. Lim, S., K. Y. Lee, M. S. Lee, C. N. Choi, and Y. D. Kim (2001), Controlled release of indomethacin using biodegradable polymer microspheres, Korean J. Biotechnol. Bioeng. 16, 505-510
  4. Kim, B. S., I. D. Jung, J. S. Kim, J. H. Lee, I. Y. Lee, and K. B. Lee (2000), Curdlan gels as protein drug delivery vehicles, Biotechnology Letters 22, 1127-1130 https://doi.org/10.1023/A:1005636205036
  5. Na, K., K. H. Park, S. W. Kim, and Y. H. Bae (2000), Self-assembled hydtogel nanoparticles from curdlan derivatives: characterization, anti-cancer drug release and interaction with a hepatoma cell line (HepG2), J. Control. Rel. 69, 225-236 https://doi.org/10.1016/S0168-3659(00)00256-X
  6. Lee, T. K., J. S. Yang, E. S. Choi, Y. B. Yoon, S. H. Bang, K. W. Min, W. Park, and H. S. Kim (1992) Effect of short-term oral administration of indomethacin on intestinal permeability in men, Kor. J. Gastroenterol. 24, 989-995
  7. Park, Y. I., K. H. Yu, Y. S. Hong, J. W. Lee, and S. K. Kim (1998), The Furosemide Effect on renal blood flow of cats treated with indomethacin, Kor. J. Nephrol. 17, 391-400
  8. Na, K., Y. I. Jeong, and K. Y. Lee (1997), Releae of indomethacin from pH-sesitive pullulan acetate microsphere, Biotechnol. Bioprocess. Eng. 2, 48-52 https://doi.org/10.1007/BF02932463
  9. Na, K. and K. Y. Lee (1998), pH sensitive release of indomethacin using lactan-acetate microspheres, Drug Develop. Indust. Pharm. 24, 563-568 https://doi.org/10.3109/03639049809085659
  10. Lee, C. M., D. W. Kim, H. C. Lee, and K. Y. Lee (2004), Pectin microspheres for oral colon delivery: Preparation using spray dtying method and in vitro release of indomethacin, Biotechnol. Bioprocess. Eng. 9, 191-195 https://doi.org/10.1007/BF02942291
  11. Brondsted, H. and J. Kopecek (1992), Hydtogels for site-specific drug delivery to the colon: in vitro and in vivo degradation, Pharm. Res. 9, 1540-1545 https://doi.org/10.1023/A:1015847921435
  12. Lamprecht, Alf, H. Yamamoto, H. Takeuchi, and Y. Kawashima (2004), Design of pH-sensitive microspheres for the colonic delivery of the immunosuppressive drug tacrolimus, Euro. J. Pharm. Biopharm. 58, 37-43 https://doi.org/10.1016/j.ejpb.2004.01.003
  13. Yang, L., J. S. Chu, and J. A. Fix (2002), Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation, Int. J. Pharm. 235, 1-15 https://doi.org/10.1016/S0378-5173(02)00004-2