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

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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.

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References

  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).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  9. R. Waksman, A. E. Raizner, A. C. Yeung, A. J. Lansky, and L. Vandertie, Lancet, 359, 551 (2002).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  14. N. Hamada, M. Miyata, H. Eto, T. Shirasawa, Y. Akasaki, A. Nagaki, and C. Tei, Atherosclerosis, 208, 97 (2010).

    Article  CAS  Google Scholar 

  15. S. N. Sehgal, H. Baker, and C. Vézina, J. Antibiot., 28, 727 (1975).

    Article  CAS  Google Scholar 

  16. C. Vézina, A. Kudelski, and S. N. Sehgal, J. Antibiot., 28, 721 (1975).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  18. S. N. Sehgal, Clin. Biochem., 31, 335 (1998).

    Article  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  20. A. C. Webster, R. C. Woodroffe, R. S. Taylor, J. R. Chapman, and J. C. Craig, BMJ, 331, 810 (2005).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  32. J. Daemen and P. W. Serruys, Circulation, 116, 316 (2007).

    Article  Google Scholar 

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Correspondence to Myung Ho Jeong.

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Park, D.S., Park, JK., Jeong, M.H. et al. Tacrolimus-eluting stent with biodegradable polymer is more effective than sirolimus- and everolimus-eluting stent in rabbit iliac artery restenosis model. Macromol. Res. 23, 1034–1041 (2015). https://doi.org/10.1007/s13233-015-3139-5

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