Polymer(Korea) (폴리머)

The Polymer Society of Korea (한국고분자학회)
권호 표지

Inhibition of Intimal Hyperplasia by Perivascular Delivery of Paclitaxel Using Poly(n-butylmethacrylate) or Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in Balloon-Injured Rat Carotid Arteries

쥐 경동맥 손상 모델에서 Poly(n-butylmethacrylate) 혹은 Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)를 이용한 Paclitaxel 국소 전달 요법의 신생내막 형성 억제 효과

  • Kwon, Jin-Sook (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Lee, Ho-Yeon (Department of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Heo, Shin-Haeng (Department of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Park, Rho-Kwan (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Shim, Tae-Jin (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Kim, Yu-Kyug (Department of Internal Medicine, College of Medicine, Chungbuk National University) ;
  • Kim, Beom-Soo (Department of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Kim, Dong-Woon (Department of Internal Medicine, College of Medicine, Chungbuk National University)
  • 권진숙 (충북대학교 의과대학 내과학교실) ;
  • 이호연 (충북대학교 공과대학 화학공학부) ;
  • 허신행 (충북대학교 공과대학 화학공학부) ;
  • 박노관 (충북대학교 의과대학 내과학교실) ;
  • 심태진 (충북대학교 의과대학 내과학교실) ;
  • 김유경 (충북대학교 의과대학 내과학교실) ;
  • 김범수 (충북대학교 공과대학 화학공학부) ;
  • 김동운 (충북대학교 의과대학 내과학교실)
  • Published : 2008.05.30
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Abstract

Polymer is a critical component of local drug delivery to prevent restenosis. This study tested whether poly(n-butylmethacrylate)(PBMA) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(PHA) was candidates for this purpose. In vitro release of paclitaxel from PBMA and PHA loaded with 10% paclitaxel exhibited a triphasic release profile, with a fast initial and intermediate second phase followed by a slow release phase. Perivascular delivery of paclitaxel using these films inhibited neointimal hyperplasia in balloon-injured rat carotid arteries. The paclitaxel-loaded PBMA or PHA groups showed significant neointimal formation reductions versus the control groups (PBMA vs control: $0.03{\pm}0.02$ vs $0.10{\pm}0.01\;mm^2$, p<0.05; PHA vs control: $0.04{\pm}0.03$ vs $0.09{\pm}0.01\;mm^2$, p<0.05). This study suggests that PBMA and PHA could be good candidate polymers of local drug delivery to prevent restenosis. Perivascular delivery using these films represents a possible approach for prevention of restenosis. These can be candidate polymers for drug eluting stents.

Poly(n-butylmethacrylate)(PBMA)와 poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(PHA)가 혈관 협착 방지를 위한 국소 약물 요법시 유용한 고분자인지 검정하였다. 10% paclitaxel 함유 필름으로부터 방출되는 paclitaxel은 초기 1주간은 빠르게, 30일까지는 중증도로, 이후는 천천히 방출되었다. Paclitaxel 함유 필름들은 풍선 손상을 가한 쥐 경동맥의 신생내막 증식을 억제하였다(PBMA vs control : $0.03{\pm}0.02$ vs $0.10{\pm}0.01\;mm^2$, p<0.05; PHA vs control: $0.04{\pm}0.03$ vs $0.09{\pm}0.01\;mm^2$, p<0.05). PBMA와 PHA는 혈관 협착 방지를 위한 약물 전달 고분자로 유용할 것으로 사료된다. 고분자 필름은 혈관 외벽에 장착이 용이한 경우 사용될 수 있다. 또한, 이 고분자들은 약물 방출 스텐트 개발시 이용될 수 있다.

Keywords

References

  1. J. J. Popma, R. M. Califf, and E. J. Topol, Circulation, 84, 1426 (1991) https://doi.org/10.1161/01.CIR.84.3.1426
  2. P. de Groote, C. Bauters, E. P. McFadden, J. M. Lablanche, F. Leroy, and M. E. Bertrand, Circulation, 91, 968 (1995) https://doi.org/10.1161/01.CIR.91.4.968
  3. J. S. Forrester, M. Fishbein, R. Helfant, and J. Fagin, J. Am. Coll. Cardiol., 17, 758 (1991) https://doi.org/10.1016/S0735-1097(10)80196-2
  4. J. W. Currier and D. P. Faxon, J. Am. Coll. Cardiol., 25, 516 (1995) https://doi.org/10.1016/0735-1097(95)98445-J
  5. A. Farb, P. F. Heller, S. Shroff, L. Cheng, F. D. Kolodgie, A. J. Carter, D. S. Scott, J. Froehlich, and R. Virmani, Circulation, 104, 473 (2001) https://doi.org/10.1161/hc3001.092037
  6. A. Gershlick, I. De Scheerder, B. Chevalier, A. Stephens-Lloyd, E. Camenzind, C. Vrints, N. Reifart, L. Missault, J. J. Goy, J. A. Brinker, A. E. Raizner, P. Urban, and A. W. Heldman, Circulation, 109, 487 (2004) https://doi.org/10.1161/01.CIR.0000109694.58299.A0
  7. D. R. Holmes, Jr., M. B. Leon, J. W. Moses, J. J. Popma, D. Cutlip, P. J. Fitzgerald, C. Brown, T. Fischell, S. C. Wong, M. Midei, D. Snead, and R. E. Kuntz, Circulation, 109, 634 (2004) https://doi.org/10.1161/01.CIR.0000112572.57794.22
  8. S. J. Park, W. H. Shim, D. S. Ho, A. E. Raizner, S. W. Park, M. K. Hong, C. W. Lee, D. Choi, Y. Jang, R. Lam, N. J. Weissman, and G. S. Mintz, N. Engl. J. Med., 348, 1537 (2003) https://doi.org/10.1056/NEJMoa021007
  9. J.-S. Kwon, S.-S. Park, Y.-G. Kim, J.-H. Son, Y.-S. Lee, K. S. Kim, K.-K. Hwang, D.-W. Kim, and M.-C. Cho, Korean Circ. J., 35, 221 (2005) https://doi.org/10.4070/kcj.2005.35.3.221
  10. J.-S. Park, J.-H. Shin, D.-H. Lee, J.-M. Rhee, M.-S. Kim, H.-B. Lee, and G.-S. Khang, Polymer(Korea), 31, 201 (2007)
  11. S. H. Kim, K.-S. Lee, Y. H. Kim, W. J. Choi, B. S. Kim, E.-G. Kim, and D. S. Kim, Polymer(Korea), 31, 153 (2007)
  12. H.-S. Kim, J. S. Kim, D.-W. Kim, B. C. Kang, B. H. Lee, and B. S. Kim, Korean J. Biotechnol. Bioeng., 18, 107 (2003)
  13. J. S. Kim, B. H. Lee, and B. S. Kim, Biochem. Eng. J., 23, 169 (2005) https://doi.org/10.1016/j.bej.2005.01.016
  14. Y. Saito, S. Nakamura, M. Hiramitsu, and Y. Doi, Polymer Int., 39, 169 (1996) https://doi.org/10.1002/(SICI)1097-0126(199603)39:3<169::AID-PI453>3.0.CO;2-Z
  15. A. B. Dhanikula and R. Panchagnula, The AAPS J., 11, e27 (2004)
  16. J. Grant, M. Blicker, M. Piquette-Miller, and C. Allen, The Pharm. Sci., 94, 1512 (2005) https://doi.org/10.1002/jps.20379
  17. B. Kelly, M. Melhem, J. Zhang, G. Kasting, J. Li, M. Krishnamoorthy, S. Heffelfinger, S. Rudich, P. Desai, and P. Roy-Chaudhury, Nephrol. Dial. Transplant., 21, 2425 (2006) https://doi.org/10.1093/ndt/gfl250
  18. N. M. Pires, B. L. van der Hoeven, M. R. de Vries, L. M. Havekes, B. J. van Vlijmen, W. E. Hennink, P. H. Quax, and J. W. Jukema, Biomaterials, 26, 5386 (2005) https://doi.org/10.1016/j.biomaterials.2005.01.063
  19. T. Masaki, R. Rathi, G. Zentner, J. K. Leypoldt, S. F. Mohammad, G. L. Burns, L. Li, S. Zhuplatov, 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
  20. J. K. Jackson, J. Smith, K. Letchford, K. A. Babiuk, L. Machan, P. Signore, W. L. Hunter, K. Wang, and H. M. Burt, Int. J. Pharm., 283, 97 (2004) https://doi.org/10.1016/j.ijpharm.2004.06.025
  21. S. C. Goodwin, H. C. Yoon, G. Chen, P. Abdel-Sayed, M. M. Costantino, S. M. Bonilla, and E. Nishimura, Cardiovasc. Intervent. Radiol., 26, 158 (2003) https://doi.org/10.1007/s00270-002-2562-0
  22. W. J. van der Giessen, A. M. Lincoff, R. S. Schwartz, H. M. M. van Beusekom, P. W. Serruys, D. R. Holmes, Jr., S. G. Ellis, and E. J. Topol, Circulation, 94, 1690 (1996) https://doi.org/10.1161/01.CIR.94.7.1690
  23. G. Acharya and K. Park, Adv. Drug Deliver. Rev., 58, 387 (2006) https://doi.org/10.1016/j.addr.2006.01.016
  24. S. F. Williams and D. P. Martin, "Applications of PHAs in medicine and pharmacy", in Biopolymers, Polyesters III, Y. Doi and A. Steinbuchel, Editors, Wiley-VCH, Weinheim, p. 91 (2002)
  25. C. W. Hwang, D. Wu, and E. R. Edelman, Circulation, 104, 600 (2001) https://doi.org/10.1161/hc3101.092214
  26. A. Finkelstein, D. McClean, S. Kar, K. Takizawa, K. Varghese, N. Baek, K. Park, M. C. Fishbein, R. Makkar, F. Litvack, and N. L. Eigler, Circulation, 107, 777 (2003) https://doi.org/10.1161/01.CIR.0000050367.65079.71
  27. C. J. Creel, M. A. Lovich, and E. R. Edelman, Circ. Res., 86, 879 (2000) https://doi.org/10.1161/01.RES.86.8.879