DOI QR코드

DOI QR Code

Paclitaxel Coating on ePTFE Artificial Graft and the Release Behavior

ePTFE 인공혈관에 대한 파클리탁셀의 코팅 및 방출거동

  • Lim, Soon-Yong (Department of Polymer Science and Engineering, Kumoh National Institute of Technology) ;
  • Kim, Cheol-Joo (Department of Polymer Science and Engineering, Kumoh National Institute of Technology) ;
  • Kim, Eun-Jin (Institute of Interventional Medicine, M.I.Tech Co., Ltd.) ;
  • Kwon, Oh-Kyoung (Gastric Cancer Center, Kyungpook National University Medical Center) ;
  • Kwon, Oh-Hyeong (Department of Polymer Science and Engineering, Kumoh National Institute of Technology)
  • 임순용 (금오공과대학교 고분자공학과) ;
  • 김철주 (금오공과대학교 고분자공학과) ;
  • 김은진 ((주)엠아이텍) ;
  • 권오경 (칠곡경북대학교병원 위암센터) ;
  • 권오형 (금오공과대학교 고분자공학과)
  • Received : 2011.10.04
  • Accepted : 2011.11.25
  • Published : 2012.05.25

Abstract

In this study, expanded poly(tetrafluoro ethylene) (ePTFE) graft was modified to be used as a hemodialysis vascular access. Biodegradable poly(D,L-lactide-$co$-glycolide) (PLGA) was coated onto the inner surface of ePTFE graft with paclitaxel, which is often used as an anti-cancer agent and for reducing neointimal hyperplasia. Surface characterization before and after PLGA coating was carried out by SEM and ATR-FTIR. Porous sturcture of ePTFE was maintained after coating of PLGA solution. The amounts of coated PLGA and paclitaxel determined by ATR-FTIR and HPLC were 1.96 and 0.263 mg/$cm^2$, respectively. Young's modulus was decreased and tensile strength was increased by PLGA coating. Released paclitaxel as a function of incubation time was monitored by HPLC. Approximately 35% of coated paclitaxel was released steadily for 4 weeks with the biodegradation of PLGA. From these results, it is expected that the effect of paclitaxel on reducing neointimal hyperplasia and stenosis is maintained for a long time.

본 연구에서는 혈액투석 시 필요한 혈관접근통로로 활용되는 expanded poly(tetrafluoro ethylene)(ePTFE) 인공혈관을 표면 개질하였다. 생분해성 합성고분자인 poly(D,L-lactide-$co$-glycolide)(PLGA)와 함께 항암제로서 뿐만아니라 항증식제제로서 널리 쓰이고 있는 파클리탁셀을 인공혈관 표면에 코팅함으로써 PLGA가 생분해됨에 따라 파클리탁셀을 서방할 수 있도록 고안하였다. 인공혈관의 다공구조 특성을 유지하면서 인공혈관 표면에 1.96 mg/$cm^2$의 PLGA가 코팅되었음을 ATR-FTIR을 통해 확인하였다. 또한 0.263 mg/$cm^2$의 파클리탁셀이 인공혈관에 코팅되었음을 HPLC로 확인하였다. PLGA를 코팅함으로써 인공혈관의 모듈러스는 감소하였으나 인장강도는 향상되었다. 약물방출 실험 결과 PLGA의 생분해거동에 동반하여 코팅된 파클리탁셀의 약 35%가 28일 동안 지속적으로 방출되었다. 이러한 지속적인 파클리탁셀의 방출은 장기간에 걸쳐 신내막 과형성증을 억제하여 혈관의 개존율을 향상시킬 것으로 기대된다.

Keywords

Acknowledgement

Grant : 안정적인 혈액투석을 위한 차세대 인공혈관의 실용화 기술개발

Supported by : 보건복지부

References

  1. American Heart Association 1997 Heart and stroke statistical update: American Heart Association, National Center, Dallas, 1997.
  2. R. Langer and J. P. Vacanti, Science, 260, 920 (1993). https://doi.org/10.1126/science.8493529
  3. B. H. Lee, H. Y. Nam, T. Kwon, S. J. Kim, G. Y. Kwon, H. J. Jeon, H. J. Lim, W. K. Lee, J.-S. Park, J. Y. Ko, and D. J. Kim, Nephrol. Dial. Transpl., 21, 2432 (2006). https://doi.org/10.1093/ndt/gfl070
  4. T. S. Huber J. W. Carter, R. L. Carter, and J. M. Seeger, J. Vasc. Surg., 38, 1005 (2003). https://doi.org/10.1016/S0741-5214(03)00426-9
  5. T. Masaki, R. Rathi, G. Zentner, J. K. Leypoldt, S. F. Mohammad, G. L. Burns, L. Li, Z. Sergey, T. Chirananthavat, S.-J. Kim, S. Kern, J. Holman, S. W. Kim, and A. K. Cheung, Kidney Int., 66, 2061 (2004). https://doi.org/10.1111/j.1523-1755.2004.00985.x
  6. T. R. Kohler, P. M. Toleikis, D. M. Gravett, and R. L. Avelar, J. Vasc. Surg., 45, 1029 (2007). https://doi.org/10.1016/j.jvs.2007.01.057
  7. L. Matyas, M. Berry, G. Menyhei, L. Tamas, G. Acsady, P. Cuypers, F. Halmos, A. C. de Vries, V. Forgacs, G. Ingenito, and R. Avelar, Eur. J. Vasc. Endovasc. Surg., 35, 715 (2008). https://doi.org/10.1016/j.ejvs.2007.11.024
  8. B. H. Lee, J. E. Lee, K. W. Lee, H. Y. Nam, H. J. Jeon, Y. J. Sung, J. S. Kim, H. J. Lim, J.-S. Park, J. Y. Ko, and D. J. Kim, Nephrol. Dial. Transpl., 22, 2800 (2007). https://doi.org/10.1093/ndt/gfm438
  9. R. Y. Kanterman, T. M. Vesely, T. K. Pilgram, B. W. Guy, D. W. Windus, and D. Picus, Radiology, 195, 135 (1995). https://doi.org/10.1148/radiology.195.1.7892454
  10. M. Z. Amin and T. M. Vesely, J. Vasc. Interv. Radiol., 15, 589 (2004). https://doi.org/10.1097/01.RVI.00000127897.23424.E5
  11. A. J. Sorom, C. B. Hughes, J. T. McSarthy, B. M. Jenson, M. Prieto, J. M. Panneton, S. Sterioff, M. D. Stegall, and S. L. Nyberg, Surgery, 132, 135 (2002). https://doi.org/10.1067/msy.2002.124932
  12. E. Grube, S. Silber, K. E. Hauptmann, R. Mueller, L. Buellesfeld, U. Gerckens, and M. E. Russell, Circulation, 107, 38 (2003). https://doi.org/10.1161/01.CIR.0000047700.58683.A1
  13. A. Colombo, J. Drzewiecki, A. Banning, E. Grube, K. Hauptmann, S. Silber, D. Dudek, S. Fort, F. Schiele, K. Zmudka, G. Guagliumi, and M. E. Russell, Circulation, 108, 788 (2003). https://doi.org/10.1161/01.CIR.0000086926.62288.A6
  14. J. Aoki, A. Colombo, D. Dudek, A. P. Banning, J. Drzewiecki, K. Zmudka, F. Schiele, M. E. Russell, J. Koglin, and P. W. Serruys, Circulation, 112, 3876 (2005). https://doi.org/10.1161/CIRCULATIONAHA.105.558601
  15. G. W. Stone, S. G. Ellis, D. A. Cox, J. Hermiller, C. O'Shaughnessy, J. T. Mann, M. Turco, R. Caputo, P. Bergin, J. Greenberg, J. J. Popma, and M. E. Russell, New Engl. J. Med., 350, 221 (2004). https://doi.org/10.1056/NEJMoa032441
  16. G. W. Stone, S. G. Ellis, D. A. Cox, J. Hermiller, C. O'Shaughnessy, J. T. Mann, M. Turco, R. Caputo, P. Bergin, J. Greenberg, J. J. Popma, and M. E. Russell, Circulation, 109, 1942 (2004). https://doi.org/10.1161/01.CIR.0000127110.49192.72
  17. G. W Stone, S. G. Ellis, L. Cannon, J. T. Mann, J. D. Greenberg, D. Spriggs, C. O'Shaughnessy, S. DeMaio, P. Hall, J. J. Popma, J. Koglin, and M. E Russell, J. Am. Med. Assoc., 294, 1215 (2005). https://doi.org/10.1001/jama.294.10.1215
  18. S. S. Lee, J. H. Shin, J. M. Han, C. H. Cho M.-H. Kim, S.-K. Lee, J.-H. Kim, K.-R. Kim, K. M. Shin, Y. H. Won, and H.-Y. Song, Gastrointest. Endosc., 69, 1140 (2009). https://doi.org/10.1016/j.gie.2008.08.005
  19. K. L. Sullivan, A. Besarab, J. Bonn, M. J. Shapiro, G. A. Gardiner Jr., and M. J. Moritz, Radiology, 186, 867 (1993). https://doi.org/10.1148/radiology.186.3.8430200
  20. L.-M. Deng, Y.-Z. Wang, K.-K. Yang, X.-L. Wang, Q. Zhou, and S.-D. Ding, Acta Mater., 51, 5871 (2004).
  21. T. G. Park, J. Control. Release, 30, 161 (1994). https://doi.org/10.1016/0168-3659(94)90263-1
  22. T. G. Park, Biomaterials, 16, 1123 (1995). https://doi.org/10.1016/0142-9612(95)93575-X
  23. T. G. Park, W. Lu, and G. Crotts, J. Control. Release, 33, 211 (1995).
  24. T. G. Park and J.-J. Yoon, Polym. Sci. Tech., 10, 722 (1999).
  25. I. Baek, Y. J. Lee, S. J. Park, C. Z. Bai, J.-S Park, and D. J. Kim, Bull. Korean Chem. Soc., 31, 281 (2010). https://doi.org/10.5012/bkcs.2010.31.02.281