Macromolecular Research

, Volume 23, Issue 11, pp 1034–1041 | Cite as

Tacrolimus-eluting stent with biodegradable polymer is more effective than sirolimus- and everolimus-eluting stent in rabbit iliac artery restenosis model

  • Dae Sung Park
  • Jun-Kyu Park
  • Myung Ho Jeong
  • In-Ho Bae
  • So-Youn Lee
  • Eun Jae Jang
  • Kyung-Seob Lim
  • Jong Min Kim
  • Jung Ha Kim
  • Dae Young Hyun
  • Yun Ah Jeong
  • Hyun Kuk Kim
  • Doo Sun Sim
Article

Abstract

Drug-eluting stents, which are widely used in percutaneous coronary intervention, are fabricated with various considerations, such as drugs, design, polymers, and coating techniques. The aim of this study was to compare tacrolimus-eluting stents (TES), sirolimus-eluting stents (SES) and everolimus-eluting stents (EES) under identical conditions. Poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer was used to coat bare metal stents (Chonnam National University Hospital Stent, CNUH Stent) with the drugs in all fabricating procedures with an ultrasonic stent-coating machine. Surface morphologies of the stents were investigated by scanning electron microscopy. The effect of drugs released from stents on rat smooth muscle and human umbilical vein endothelial cells was examined by MTT assay. The stents were implanted in rabbit iliac arteries randomly, with either TES (n=10), SES (n=10), or EES (n=10). After six weeks of implantation, the stents were isolated and subjected to histopathological analysis. Cell viability decreased in a dose-dependent manner. The surface morphologies of the stents showed a smooth and uniform shape. The release patterns of the stents showed similar profiles over 30 days. There were no significant differences in the injury score, internal elastic lamina, lumenal area, neointimal area, percent area stenosis, and inflammation score among the three groups. However, there was a significant difference in the fibrin score (0.6±0.44 in the TES, vs. 0.8±0.48 in the SES, vs. 0.8±0.61 in the EES, n=10, p<0.05). This study showed that tacrolimus was not inferior to sirolimus (SRL) and everolimus (EVL). Moreover, tacrolimus (TCL) is more effective in decreasing the fibrin score. Therefore, tacrolimus can be a useful alternative drug for fabricating drug-eluting stents.

Keywords

tacrolimus sirolimus everolimus stent restenosis 

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References

  1. (1).
    D. E. Cutlip, M. S. Chauhan, D. S. Baim, K. K. Ho, J. J. Popma, J. P. Carrozza, D. J. Cohen, and R. E. Kuntz, J. Am. Coll. Cardiol., 40, 2082 (2002).CrossRefGoogle Scholar
  2. (2).
    R. M. Califf, D. F. Fortin, D. J. Frid, W. R. Harlan 3rd, E. M. Ohman, J. R. Bengtson, C. L. Nelson, J. E. Tcheng, D. B. Mark, and R. S. Stack, J. Am. Coll. Cardiol., 17, 2B (1991).CrossRefGoogle Scholar
  3. (3).
    M. A. Grise, V. Massullo, S. Jani, J. J. Popma, R. J. Russo, R. A. Schatz, E. M. Guarneri, S. Steuterman, D. A. Cloutier, M. B. Leon, P. Tripuraneni, and P. S. Teirstein, Circulation, 105, 2737 (2002).CrossRefGoogle Scholar
  4. (4).
    J. J. Popma, M. Suntharalingam, A. J. Lansky, R. R. Heuser, B. Speiser, P. S. Teirstein, V. Massullo, T. Bass, R. Henderson, S. Silber, P. von Rottkay, R. Bonan, K. K. Ho, A. Osattin, and R. E. Kuntz, Circulation, 106, 1090 (2002).CrossRefGoogle Scholar
  5. (5).
    I. P. Kay, A. J. Wardeh, K. Kozuma, D. P. Foley, A. H. Knook, A. Thury, G. Sianos, W. J. van der Giessen, P. C. Levendag, and P. W. Serruy, Circulation, 103, 14 (2001).CrossRefGoogle Scholar
  6. (6).
    M. B. Leon, P. S. Teirstein, J. W. Moses, P. Tripuraneni, A. J. Lansky, S. Jani, S. C. Wong, D. Fish, S. Ellis, D. R. Holmes, D. Kerieakes, and R. E. Kuntz, N. Engl. J. Med., 344, 250 (2001).CrossRefGoogle Scholar
  7. (7).
    R. Waksman, R. L. White, R. C. Chan, B. G. Bass, L. Geirlach, G. S. Mintz, L. F. Satler, R. Mehran, P. W. Serruys, A. J. Lansky, P. Fitzgerald, B. Bhargava, K. M. Kent, A. D. Pichard, and M. B. Leon, Circulation, 101, 2165 (2000).CrossRefGoogle Scholar
  8. (8).
    R. Waksman, B. Bhargava, L. White, R. C. Chan, R. Mehran, A. J. Lansky, G. S. Mintz, L. F. Satler, A. D. Pichard, M. B. Leon, and K. K. Kent, Circulation, 101, 1895 (2000).CrossRefGoogle Scholar
  9. (9).
    R. Waksman, A. E. Raizner, A. C. Yeung, A. J. Lansky, and L. Vandertie, Lancet, 359, 551 (2002).CrossRefGoogle Scholar
  10. (10).
    J. E. Sousa, M. A. Costa, A. Abizaid, A. S. Abizaid, F. Feres, I. M. Pinto, A. C. Seixas, R. Staico, L. A. Mattos, A. G. Sousa, R. Falotico, J. Jaeger, J. J. Popma, and P. W. Serruys, Circulation, 103, 192 (2001).CrossRefGoogle Scholar
  11. (11).
    M. C. Morice, P. W. Serruys, J. E. Sousa, J. Fajadet, E. Ban Hayashi, M. Perin, A. Colombo, G. Schuler, P. Barragan, G. Guagliumi, F. Molnàr, and R. Falotico, N. Engl. J. Med., 346, 1773 (2002).CrossRefGoogle Scholar
  12. (12).
    F. Saia, P. A. Lemos, C. A. Arampatzis, A. Hoye, M. Degertekin, K. Tanabe, G. Sianos, P. C. Smits, W. J. van der Giessen, P. J. de Feyter, R. T. van Domburg, and P. W. Serruys, Heart, 90, 1183 (2004).CrossRefGoogle Scholar
  13. (13).
    G. W. Stone, M. Midei, W. Newman, M. Sanz, J. B. Hermiller, J. Williams, N. Farhat, K. W. Mahaffey, D. E. Cutlip, P. J. Fitzgerald, P. Sood, X. Su, and A. J. Lansky, JAMA, 299, 1903 (2008).CrossRefGoogle Scholar
  14. (14).
    N. Hamada, M. Miyata, H. Eto, T. Shirasawa, Y. Akasaki, A. Nagaki, and C. Tei, Atherosclerosis, 208, 97 (2010).CrossRefGoogle Scholar
  15. (15).
    S. N. Sehgal, H. Baker, and C. Vézina, J. Antibiot., 28, 727 (1975).CrossRefGoogle Scholar
  16. (16).
    C. Vézina, A. Kudelski, and S. N. Sehgal, J. Antibiot., 28, 721 (1975).CrossRefGoogle Scholar
  17. (17).
    F. V. Ritacco, E. I. Graziani, M. Y. Summers, T. M. Zabriskie, K. Yu, V. S. Bernan, G. T. Carter, and M. Greenstein, Appl. Environ. Microbiol., 71, 1971 (2005).CrossRefGoogle Scholar
  18. (18).
    S. N. Sehgal, Clin. Biochem., 31, 335 (1998).CrossRefGoogle Scholar
  19. (19).
    M. Degertekin, E. Regar, K. Tanabe, P. Lemos, C. H. Lee, P. Smits, P. de Feyter, N. Bruining, E. Sousa, A. Abizaid, J. Ligthart, and P. W. Serruys, Am. J. Cardiol., 91, 1046 (2003).CrossRefGoogle Scholar
  20. (20).
    A. C. Webster, R. C. Woodroffe, R. S. Taylor, J. R. Chapman, and J. C. Craig, BMJ, 331, 810 (2005).CrossRefGoogle Scholar
  21. (21).
    C. M. Matter, I. Rozenberg, A. Jaschko, H. Greutert, D. J. Kurz, S. Wnendt, B. Kuttler, H. Joch, J. Grünenfelder, G. Zünd, F. C. Tanner, and T. F. Lüscher, J. Cardiovasc. Pharmacol., 48, 286 (2006).CrossRefGoogle Scholar
  22. (22).
    W. Schuler, R. Sedrani, S. Cottens, B. Häberlin, M. Schulz, H. J. Schuurman, G. Zenke, H. G. Zerwes, and M. H. Schreier, Transplantation, 64, 36 (1997).CrossRefGoogle Scholar
  23. (23).
    J. M. Siller-Matula, I. Tentzeris, B. Vogel, S. Schacherl, R. Jarai, A. Geppert, G. Unger, and K. Huber, Clin. Res. Cardiol., 99, 645 (2010).CrossRefGoogle Scholar
  24. (24).
    A. Giordano, S. Romano, M. Monaco, A. Sorrentino, N. Corcione, A. L. Di Pace, P. Ferraro, G. Nappo, M. Polimeno, and M. F. Romano, Am. J. Physiol. Heart Circ. Physiol., 302, H135 (2012).CrossRefGoogle Scholar
  25. (25).
    T. Kimura, T. Morimoto, M. Natsuaki, H. Shiomi, K. Igarashi, K. Kadota, K. Tanabe, Y. Morino, T. Akasaka, Y. Takatsu, H. Nishikawa, Y. Yamamoto, Y. Nakagawa, Y. Hayashi, M. Iwabuchi, H. Umeda, K. Kawai, H. Okada, K. Kimura, C. A. Simonton, and K. Kozuma, Circulation, 126, 1225 (2012).CrossRefGoogle Scholar
  26. (26).
    K. S. Lim, I. H. Bae, J. H. Kim, D. S. Park, J. M. Kim, J. H. Kim, D. S. Sim, Y. J. Hong, and M. H. Jeong, Chonnam Med. J., 49, 7 (2013).CrossRefGoogle Scholar
  27. (27).
    I. H. Bae, K. S. Lim, J. K. Park, D. S. Park, S. Y. Lee, E. J. Jang, M. S. Ji, D. S. Sim, Y. J. Hong, Y. Ahn, J. C. Park, J. G. Cho, J. C. Kang, I. S. Kim, J. W. Nah, and M. H. Jeong, J. Ind. Eng. Chem., 21, 1295 (2015).CrossRefGoogle Scholar
  28. (28).
    J. K. Park, D. G. Kim, I. H. Bae, K. S. Lim, M. H. Jeong, C. Choi, S. K. Choi, S. C. Kim, and J. W. Nah, Macromol. Res., 23, 237 (2015).CrossRefGoogle Scholar
  29. (29).
    R. S. Schwartz, E. Edelman, R. Virmani, A. Carter, J. F. Granada, G. L. Kaluza, N. A. Chronos, K. A. Robinson, R. Waksman, J. Weinberger, G. J. Wilson, and R. L. Wilensky, Circ. Cardiovasc. Interv., 1, 143 (2008).CrossRefGoogle Scholar
  30. (30).
    M. J. Suttorp, G. J. Laarman, B. M. Rahel, J. C. Kelder, M. A. Bosschaert, F. Kiemeneij, J. M. Ten Berg, E. T. Bal, B. J. Rensing, F. D. Eefting, and E. G. Mast, Circulation, 114, 921 (2006).CrossRefGoogle Scholar
  31. (31).
    S. J. Song, K. W. Jung, Y. J. Park, M. H. Jeong, Y. S. Kim, and D. L. Cho, J. Mater. Chem., 21, 8169 (2011).CrossRefGoogle Scholar
  32. (32).
    J. Daemen and P. W. Serruys, Circulation, 116, 316 (2007).CrossRefGoogle Scholar

Copyright information

© The Polymer Society of Korea and Springer Sciene+Business Media Dordrecht 2015

Authors and Affiliations

  • Dae Sung Park
    • 1
    • 2
  • Jun-Kyu Park
    • 3
  • Myung Ho Jeong
    • 1
    • 2
  • In-Ho Bae
    • 1
    • 2
  • So-Youn Lee
    • 1
    • 2
  • Eun Jae Jang
    • 1
    • 2
  • Kyung-Seob Lim
    • 1
    • 2
  • Jong Min Kim
    • 1
    • 2
  • Jung Ha Kim
    • 1
    • 2
  • Dae Young Hyun
    • 1
    • 2
  • Yun Ah Jeong
    • 1
    • 2
  • Hyun Kuk Kim
    • 1
    • 2
  • Doo Sun Sim
    • 1
    • 2
  1. 1.Korea Cardiovascular Stent InstituteJangseong-gun, JeonnamKorea
  2. 2.The Cardiovascular Convergence Research Center of Chonnam National University Hospital Designated by Ministry of Health and WelfareGwangjuKorea
  3. 3.CGBio Co. Ltd.Jangseong-gun, JeonnamKorea

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