화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.24, No.8, 725-733, August, 2016
DOI10.1007/s13233-016-4082-9  Export Citation
Optimal coating method for a dual-layer stent with sirolimus and alpha-lipoic acid in a porcine coronary restenosis model
Kyung Seob Lim1, 2, Jun-Kyu Park3, Myung Ho Jeong4, 1, †, In-Ho Bae4, 1, Jae-Woon Nah3, Dae Sung Park1, 2, Jae-Won Sim1, 2, Jung Ha Kim1, 2, So Youn Lee4, 1, Eun Jae Jang4, 1, Suyoung Jang1, 2, Hyun Kuk Kim1, 2, Doo Sun Sim1, 2, In Soo Kim1, 2, Young Joon Hong1, 2, Youngkeun Ahn1, 2, and Jung Chaee Kang1, 2
  • 1Cardiovascular Convergence Research Center Nominated by Korea Ministry of Health and Welfare, Chonnam National University Hospital, Gwangju, 61469, Korea
  • 2Cardiovascular Research Center, Chonnam National University Hospital, Gwangju, 61469, Korea
  • 3Department of Polymer Science and Engineering, Sunchon National University, Suncheon, Jeonnam, 57940, Korea
  • 4Korea Cardiovascular Stent Research Institute, Jangsung, Jeonnam, 57248, Korea
E-mail:
The aim of this study was to evaluate the optimal method for coating a double-layer polymer coronary stent with sirolimus and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. Pigs were randomized into three groups, in which the coronary arteries (10 in each group) were stented with a dual-layer stent with an inner layer of ALA and an outer layer of sirolimus (IAOS, n=10), a dual-layer stent with an inner layer of sirolimus and an outer layer of ALA (ISOA, n=10), or a commercial drug-eluting stent (biolimus-eluting stent, BES, n=10). Histopathological analysis was performed 28 days after stenting. There were no significant differences among the three groups in injury and inflammation scores. There were significant differences among the three groups in neointimal area (1.1±0.16 mm2 for IAOS vs. 1.3±0.41 mm2 for ISOA vs. 1.9±0.50 mm2 for BES, p<0.0001), and percentage of stenosis area (21.4±3.08% for IAOS vs. 29.9±7.72% for ISOA vs. 38.2±9.08% for BES, p<0.0001). Regarding the percentage of stenosis area, microcomputed tomography revealed significant differences between the three groups (23.8±3.51% for IAOS vs. 28.9±4.65% for ISOA vs. 36.4±8.07% for BES, p<0.05). Compared with commercial stent placement, both IAOS and ISOA resulted in significant inhibition of neointimal formation in a porcine coronary restenosis model. In addition, IAOS was more effective than ISOA in preventing anti-neointimal hyperplasia after stenting.
Keywords:polymer;drug-eluting stent;sneointimal hyperplasia;percutaneous coronary;intervention;restenosis;inflammation
  1. Gruntzig A, Lancet, 1, 263 (1978)
  2. Alexander RW, N. Engl. J. Med., 331, 468 (1994)
  3. Chesebro JH, Lam JY, Badimon L, Fuster V, Am. J. Cardiol., 60, 10B (1987)
  4. Edelman ER, Rogers C, Am. J. Cardiol., 81, 4E (1998)
  5. Deuse T, Peter C, Fedak PW, Doyle T, Reichenspurner H, Zimmermann WH, Eschenhagen T, Stein W, Wu JC, Robbins RC, Schrepfer S, Circulation, 120, S247 (2009)
  6. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R, J. Am. Coll. Cardiol., 48, 193 (2006)
  7. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K, N. Engl. J. Med., 334, 1084 (1996)
  8. Togni M, Raber L, Cocchia R, Wenaweser P, Cook S, Windecker S, Meier B, Hess OM, Int. J. Cardiol., 120, 212 (2007)
  9. Yazdani SK, Vorpahl M, Nakano M, Su SH, Kolodgie FD, Virmani R, EuroIntervention, 7, 835 (2011)
  10. Vasquez EM, Am. J. Health Syst. Pharm., 57, 437 (2000)
  11. Muthukkumar S, Ramesh TM, Bondada S, Transplantation, 60, 264 (1995)
  12. Packer L, Roy S, Sen CK, Adv. Pharmacol., 38, 79 (1997)
  13. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA, Diabet. Med., 21, 114 (2004)
  14. Sung MJ, Kim W, Ahn SY, Cho CH, Koh GY, Moon SO, Kim DH, Lee S, Kang KP, Jang KY, Park SK, Circ. Res., 97, 880 (2005)
  15. Lee KM, Park KG, Kim YD, Lee HJ, Kim HT, Cho WH, Kim HS, Han SW, Koh GY, Park JY, Lee KU, Kim JG, Lee IK, Atherosclerosis, 189, 106 (2006)
  16. Bae IH, Lim KS, Park JK, Park DS, Lee SY, Jang EJ, Ji MS, Sim DS, Hong YJ, Ahn Y, Park JC, Cho JG, Kang JC, Kim IS, Nah JW, Jeong MH, J. Ind. Eng. Chem., 21, 1295 (2015)
  17. Lim KS, Bae IH, Kim JH, Park DS, Kim JM, Kim JH, Sim DS, Hong YJ, Jeong MH, Chonnam. Med. J., 49, 7 (2013)
  18. Schwartz RS, Huber KC, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, Holmes DR, J. Am. Coll. Cardiol., 19, 267 (1992)
  19. Che HL, Bae IH, Lim KS, Song IT, Lee H, Muthiah M, Namgung R, Kim WJ, Kim DG, Ahn Y, Jeong MH, Park IK, Biomaterials, 33, 8548 (2012)
  20. Schwartz RS, Edelman E, Virmani R, Carter A, Granada JF, Kaluza GL, Chronos NA, Robinson KA, Waksman R, Weinberger J, Wilson GJ, Wilensky RL, Circ. Cardiovasc. Interv., 1, 143 (2008)
  21. Suzuki T, Kopia G, Hayashi S, Bailey LR, Llanos G, Wilensky R, Klugherz BD, Papandreou G, Narayan P, Leon MB, Yeung AC, Tio F, Tsao PS, Falotico R, Carter AJ, Circulation, 104, 1188 (2001)
  22. Ma X, Oyamada S, Gao F, Wu T, Robich MP, Wu H, Wang X, Buchholz B, McCarthy S, Gu Z, Bianchi CF, Sellke FW, Laham R, J. Pharm. Biomed. Anal., 54, 807 (2011)
  23. Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, Pichard AD, Kent KM, Stone GW, Leon MB, Circulation, 100, 1872 (1999)
  24. Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schomig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabate M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, Petronio AS, Nordmann AJ, D, Lancet, 370, 937 (2007)
  25. Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB, N. Engl. J. Med., 356, 998 (2007)
  26. Pendyala LK, Li J, Shinke T, Geva S, Yin X, Chen JP, King SB, 3rd, Robinson KA, Chronos NA, Hou D, JACC Cardiovasc. Interv., 2, 253 (2009)
  27. Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R, Arterioscler. Thromb. Vasc. Biol., 27, 1500 (2007)
  28. Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD, Circulation, 109, 701 (2004)
  29. Cook S, Ladich E, Nakazawa G, Eshtehardi P, Neidhart M, Vogel R, Togni M, Wenaweser P, Billinger M, Seiler C, Gay S, Meier B, Pichler WJ, Juni P, Virmani R, Windecker S, Circulation, 120, 391 (2009)
  30. Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R, Circulation, 118, 1138 (2008)
  31. Tamai H, Igaki K, Kyo E, Kosuga K, Kawashima A, Matsui S, Komori H, Tsuji T, Motohara S, Uehata H, Circulation, 102, 399 (2000)
  32. Nishio S, Kosuga K, Igaki K, Okada M, Kyo E, Tsuji T, Takeuchi E, Inuzuka Y, Takeda S, Hata T, Takeuchi Y, Kawada Y, Harita T, Seki J, Akamatsu S, Hasegawa S, Bruining N, Brugaletta S, de Winter S, Muramatsu T, Onuma Y, Serruys PW, Ikeguchi S, Circulation, 125, 2343 (2012)
  33. Ahmed TA, Bergheanu SC, Stijnen T, Plevier JW, Quax PH, Jukema JW, EuroIntervention, 7, 505 (2011)
  34. Klauss V, Serruys PW, Pilgrim T, Buszman P, Linke A, Ischinger T, Eberli F, Corti R, Wijns W, Morice MC, di Mario C, van Geuns RJ, van Es GA, Kalesan B, Wenaweser P, Juni P, Windecker S, JACC Cardiovasc. Interv.
  35. Herrmann J, Bodmeier R, Eur. J. Pharm. Biopharm., 45, 75 (1998)
  36. Lin SY, Ho LT, Chiou HL, Biomater. Med. Devices Artif. Organs, 13, 187 (1985)
  37. Kawai F, Yamanaka H, Arch. Microbiol., 146, 125 (1986)
  38. Khan W, Farah S, Nyska A, Domb AJ, J. Control. Release, 168, 70 (2013)
  39. Garg S, Serruys PW, J. Am. Coll. Cardiol., 56, S43 (2010)
  40. Thipparaboina R, Khan W, Domb AJ, Int. J. Pharm., 454, 4 (2013)
  41. Gummert JF, Ikonen T, Morris RE, J. Am. Soc. Nephrol., 10, 1366 (1999)
  42. Packer L, Witt EH, Tritschler HJ, Free Radic. Biol. Med., 19, 227 (1995)
  43. Packer L, Witt EH, Tritschler HJ, Free Radic. Biol. Med., 19, 227 (1995)
  44. Kim HJ, Kim JY, Lee SJ, Oh CJ, Choi YK, Lee HJ, Do JY, Kim SY, Kwon TK, Choi HS, Lee MO, Park IS, Park KG, Lee KU, Lee IK, Arterioscler. Thromb. Vasc. Biol., 30, 2164 (2010)
  45. Lim SY, Bae EH, Jeong MH, Kim JH, Hong YJ, Sim DS, Kim YS, Park IK, Ahn Y, Song SJ, Cho DL, Kim KS, Kang JC, J. Cardiol., 54, 375 (2009)
  46. Lim KS, Hong YJ, Hachinohe D, Ahmed K, Jeong MH, Kim JH, Sim DS, Lee MG, Park KH, Ahn Y, Cho JG, Park JC, Song SJ, Jung KW, Cho DL, Kang JC, Korean Circ. J., 41, 241 (2011)
  47. Garg S, Bourantas C, Serruys PW, Nat. Rev. Cardiol., 10, 248 (2013)
  48. Malik N, Gunn J, Holt CM, Shepherd L, Francis SE, Newman CM, Crossman DC, Cumberland DC, Heart, 80, 509 (1998)