효율적인 약물 방출 스텐트 제조를 위한 고분자 코팅물질 개발

박태현; 조은애; 나건; Tae Hyun Park; Eun Ae Jo; Kun Na

Polymer(Korea), Vol.35, No.5, 483-487, September, 2011

Export Citation

효율적인 약물 방출 스텐트 제조를 위한 고분자 코팅물질 개발

Development of Polymeric Coating Material for Effective Drug-eluting Stent

박태현, 조은애, 나건^†

가톨릭대학교 생명공학부 생명공학전공

Tae Hyun Park, Eun Ae Jo, and Kun Na^†

Department of Biotechnology, The Catholic University of Korea, 43-1 Yokkok 2-dong, Wonmi-gu, Bucheon 420-743, Korea

E-mail:

초록

효율적 비혈관용 약물방출 스텐트 제조를 위해 풀루란 아세테이트(pullulan acetate, PA)가 테프론 (polytetrafluorethylene;PTFE)으로 피막된 스텐트(PTFE-stent)의 코팅재료로 연구되었다. 파크리탁셀 함유 PA가 코팅된 PTFE-stent의 표면, 약물 방출 거동, 세포독성이 측정되었으며, 동물실험을 통해 이의 가능성이 검토되었다. 전자현미경으로 표면을 관찰한 결과 표면이 PTFE 피막에 비해 훨씬 매끄러웠고, 약물은 80일 동안 서방적 방출 거동을 보였다. PA와 함께 코팅된 파크리탁셀의 안정성을 annexin V 결합 염색법을 통하여 측정한 결과 apoptosis의 비율이 천연 파크리탁셀과 유사한 것으로 보아 봉입된 파크리탁셀의 변성이 없음을 알 수 있었다. 소동물 실험에서는 파크리탁셀이 봉입된 PA-PTFE가 고형암의 성장을 억제하였다. 위의 결과로 보아 PA는 효율적 비혈관계 약물방출 스텐트 개발에 매우 유용한 물질이라고 기대된다.

For the preparation of effective non-vascular drug eluting stent (DES), pullulan acetate (PA) was investigated as a coating material for polytetrafluorethylene (PTFE)-covered stent. PA was coated on PTFE-covered stent (PTFE-stent) by dip coating technique, and then its surface morphology, drug release behavior and cellular toxicity were tested. Field emission-scanning electron microscopy (FE-SEM) result indicated that its surface was smoother after PA coating without any cracking. The sustained release behavior of paclitaxel from PA-coated PTFE membrane was observed for 80 days. Also, the biological stability of paclitaxel in the membrane was confirmed by annexin V binding assays. Furthermore, the antitumor activity was demonstrated by an in vivo test against CT-26 murine colorectal tumors. From the results, we concluded that PA was expected as a useful coating material to design an effective non-vascular DES.

Keywords:drug eluting stent;pullulan acetate;paclitaxel;sustained release.

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[1] Regan BF, U.S. Patent 4,795,458 (1989)

[2] Rulbul ZR, Bruckheimer E, Love JC, Fahey JT, Hellenbrand WE, Catheter. Cardiovasc. Diagn., 39, 36 (1996)

[3] Sheth S, Litvack F, Dev V, Fishbein MC, Forrester JS, Eigler N, Circulation., 94, 1733 (1996)

[4] Vanderburgh L, Ho CS, Prog. Cardiovasc. Dis., 39, 187 (1996)

[5] Bonan R, Asgar AW, US Cardiology., 6, 81 (2009)

[6] Shin JH, Nucl. Med. Mol. Imaging., 40, 106 (2006)

[7] Chieffo A, Colombo A, Minerva Cardioangiol 2002., 50, 419 (2002)

[8] Jeong KH, Kim YJ, Polymer(Korea)., 30, 512 (2008)

[9] Kim DM, Lee BS, Park CH, Park K, Son TI, Jeong MH, Han DK, Polym.(Korea), 34(2), 178 (2010)

[10] Wache HM, Tartakowska DJ, Hentrich A, Wagner MH, J. Mater. Sci. Mater. Med., 14, 109 (2003)

[11] Park W, Park SJ, Na K, Colloids Surf. B: Biointerfaces., 79, 501 (2010)

[12] Meng S, Liu Z, Shen L, Guo Z, Chou LL, Zhong W, Du Q, Ge J, Biomaterials., 30, 2276 (2009)

[13] Chang JH, Kim KY, Ahn SC, Kwon HY, Korea Society of Life Science., 17, 1027 (2007)

[14] Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenburg J, Popma JJ, Russell ME, New Engl. J. Med., 350, 3 (2004)

[15] Kato K, Tsuzuki A, Taoda H, Torii Y, Kato T, Butsugan Y, J. Mater. Sci., 29(22), 5911 (1994)

[16] Moon S, Yang SG, Na K, Biomaterials., 32, 3603 (2011)

[17] Na K, Jeong YI, Lee KY, Biotechnol. Bioproc. Eng., 2, 48 (1997)

[18] van Engeland M, Nieland LJW, Ramaekers FCS, Schutte B, Reutelingsperger CPM, Cytometry., 30, 1 (1998)