다양한 생체고분자로 코팅된 Paclitaxel Eluting Stent의 약물함량과 세포독성 연구

A Study of Drug Content and Cell Cytotoxicity of Paclitaxel-eluting Stents Coated with Various Biopolymer

  • 김동곤 ((주)엠아이텍 중재의학연구소) ;
  • 신일균 ((주)엠아이텍 중재의학연구소) ;
  • 김한기 ((주)엠아이텍 중재의학연구소) ;
  • 김성현 ((주)엠아이텍 중재의학연구소) ;
  • 이주호 ((주)엠아이텍 중재의학연구소) ;
  • 기병윤 ((주)엠아이텍 중재의학연구소) ;
  • 나재운 (순천대학교 공과대학 고분자공학과) ;
  • 서태석 (가톨릭대학교 의과대학 의공학교실) ;
  • 김상호 (가톨릭대학교 의과대학 의공학교실)
  • Kim, Dong-Gon (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Shin, Il-Gyun (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Kim, Gi-Han (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Kim, Seong-Hyeon (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Lee, Ju-Ho (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Ki, Byoyng-Yun (Institute of Interventional Medicine, M. I. Tech Co., Lnc) ;
  • Nah, Jae-Woon (Department of Polymer Science and Engineering, Sunchon National University) ;
  • Suh, Tae-Suk (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea) ;
  • Kim, Sang-Ho (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea)
  • 발행 : 2009.09.30

초록

본 연구는 소화기영역에서의 재협착을 방지하기 위하여 인간의 혈관 평활근 세포의 증식과 이동을 억제하며 신생내막의 형성을 억제하는 특성을 갖는 파클리탁셀(paclitaxel)을 스텐트 표면에 PVAc, PLGA, Silicone rubber 등 다양한 생체고분자로 코팅하여 paclitaxel eluting stent (PES)을 제조하고 그 특성을 분석하였다. 제조된 PES는 코팅용액의 농도가 증가할수록 그리고 코팅고분자의 분자량이 증가할수록 약물함량은 증가 되었고, bare 스텐트보다 커버드(covered) 스텐트의 표면적이 넓기 때문에 약물함량이 약 3배 정도 많음을 알 수 있었다. $^1H-NMR$ 결과에서 스텐트 표면에 파클리탁셀의 코팅과 약물의 변형이 없었음을 알 수 있었고, Silicone rubber을 제외한 다른 생체고분자는 스텐트 표면에 약물이 고르게 코팅되었음을 SEM image로부터 알 수 있었다. 그리고 in vitro에서 PES의 항암활성은 생분해성 고분자이고 분자량이 작은 PLGA 502H가 가장 높게 나타났으며, 분자량이 높을수록 낮은 항암활성을 나타냈다. 이상의 결과로부터 코팅고분자의 종류, 분자량 그리고 코팅용액의 농도를 변화시켜 약물함량을 증가시키고 약물방출을 조절할 수 있는 PES를 성공적으로 제조하였다.

In this study, the paclitaxel eluting stent (PES) was prepared by coating a biliary stent with paclitaxel using various biopolymer such as poly (vinyl acetate) (PVAc), poly (lactic-co-glycolic acid) (PLGA), Silicone rubber for restenosis prevention in gastrointestinal disease by a dip-coating method. Drug contents of PES were increased as surface area of stent, concentration and molecular weight of coating polymer increase. In $^1H-NMR$ specta, we know that drug did not change by confirming specific peaks of paclitaxel in PES. As shown in SEM image, PES prepared using various biopolymer is coated clearly and regularly except Silicone rubber coating polymer. In in vitro cell cytotoxicity test, bare stent showed low cytotoxic effect against CT-26 colon carcinoma cell line on 3 day. However, PES coated with PLGA 502H showed the highest cytotoxicity because PLGA 502H is biodegradable polymer and has less molecular weight than other coating polymer. These results suggest that PES coated various biopolymer can be prevented restenosis in gastrointestinal disease.

키워드

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