쾌속조형기법을 이용한 생분해성 스텐트용 메쉬필름의 약물방출거동 효과

정신영; 김양은; 고영주; 신왕수; 이준희; 김완두; 유영은; 박수아; Sin Young Cheong; Yang Eun Kim; Young Joo Koh; Wang Soo Shin; Jun Hee Lee; Wan Doo Kim; Young Eun Yoo; Su A Park

Polymer(Korea), Vol.38, No.1, 93-97, January, 2014

Export Citation

쾌속조형기법을 이용한 생분해성 스텐트용 메쉬필름의 약물방출거동 효과

Effect of Drug Eluting Uniformity for Biodegradable Stent by Solid Freeform Fabrication

정신영, 김양은, 고영주¹, 신왕수¹, 이준희, 김완두, 유영은, 박수아^†

한국기계연구원 나노융합기계연구본부
¹㈜삼양바이오팜 의약바이오연구소

Sin Young Cheong, Yang Eun Kim, Young Joo Koh¹, Wang Soo Shin¹, Jun Hee Lee, Wan Doo Kim, Young Eun Yoo, and Su A Park^†

Nano Convergence & Manufacturing Systems Research Division, Korea Institute of Machinery & Materials (KIMM), Daejeon 305-343, Korea
¹Medical Devices Research, R&D Center, Samyang Biopharmaceuticals Corporation, Daejeon 305-717, Korea

E-mail:

초록

약물방출 고분자 코팅 스텐트는 수술후 재협착을 획기적으로 줄였지만, 약물방출이 균일한 구조체를 제작하는 것이 어렵고 체내에 구조체를 영구적으로 남겨야 하는 부담을 여전히 가지고 있다. 이를 해결하는 방안으로 생분해성 고분자로 스텐트를 제작하는 방법들이 활발하게 연구되고 있다. 본 연구에서는 조형가공기술(solid freeform fabrication, SFF)의 하나인 쾌속조형기법(rapid prototyping technique)의 3차원 플로팅(3D plotting) 기술을 이용하여 파크리탁셀(PTX) 약물을 함유한 폴리카프로락톤(PCL) 3차원 구조체를 제작하였고, 생분해성 PCL 고분자로부터 PTX의 방출거동과 스텐트 제작 가능성을 고찰하였다. 약물을 포함한 구조체의 표면특성을 SEM으로 확인한 결과 굴곡이 자연스럽고 매끄러운 표면을 가지고 있었다. FTIR을 통해서 약물이 성공적으로 구조체에 포함되었음을 확인하였고, NMR과 HPLC를 통해서 PCL 구조체 중의 PCL함량과 PTX의 서서히 방출됨을 확인되었다. 또한 세포실험을 통해 구조체에서 방출된 약물이 생물학적으로 활성을 유지하고 있으며, 반복제작된 구조체에서도 균일한 활성의 약물이 방출됨을 확인하였다. 이와같은 쾌속조형기법을 이용하여 약물을 포함하는 구조체를 제작하고 분석함으로써, 생분해성 고분자 스텐트로서의 적용가능성을 제시하였다.

Biodegradable drug-eluting stent has dual functions of supporting the lumen and treating internal tumor preventing the restenosis by releasing drug. In this study, the polycaprolactone (PCL) based three dimensional (3D) mesh loaded with paclitaxel (PTX) was presented by rapid prototyping (RP) technique of solid freeform fabrication (SFF) for biodegradable drug-eluting stent application. PCL has many advantageous properties such as good biocompatibility, good mechanical properties, and good drug permeability. PTX is widely used in the cancer treatment by inhibiting tumor cell proliferation. Analytical methods of HPLC and NMR were used for simultaneous quantification of PTX. Scanning electron microscopy (SEM) was performed to observe the architecture and morphologies of 3D mesh. The cytotoxicity assay results indicated released PTX’s biological activity. This study provided that PCL based 3D mesh loaded with PTX by RP technique has great potential for biodegradable drug-eluting stent application.

Keywords:drug-eluting stent;polycaprolactone (PCL);paclitaxel (PTX);rapid prototyping (RP);solid freeform fabrication (SFF).

[References]

Alexis F, Venkatraman SS, Rath SK, Boey F, J. Control. Release, 98, 67 (2004)
Topol EJ, Textbook of Cardiovascular Medicine, 3rd Edition, Lippincott Williams & Wilkins, Philadelphia, PA (2007)
Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL, Am. Heart. J., 151, 1260 (2006)
Williams DO, Abbott JD, Circulation, 116, 2363 (2007)
Bosiers CCM, Deloose K, Berbist J, Peeters P, Vasc. Health Risk Manag., 4, 553 (2008)
Siablis D, Pantelis K, Karnabatidis D, Kagadis GC, Katsanos K, Tsolakis J, J. Endovasc. Ther., 12, 685 (2005)
Grant AG, White CJ, Collins TJ, Jenkins JS, Reilly JP, Ramee SR, Catherter. Cardiovasc. Interv., 71, 112 (2008)
Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Captuo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, N. Engl. J. Med., 349, 1315 (2003)
Xie J, Wang CH, Pharmaceut. Res., 23, 1817 (2006)
Zeng J, Xu X, Chen X, Liang Q, Bian X, Yang L, Jing X, J. Control. Release, 92, 227 (2003)
Liebmann J, Cook JA, Lipschultz C, Cancer Chemoth. Pharm., 33, 331 (1994)
Wessely R, Eur. Heart. J., 28, 2720 (2007)
Wang TH, Wang HS, Soong YK, Cancer Chemoth. Pharm., 88, 2619 (2000)
Fischell TA, Circulation, 94, 1494 (1996)
Pham DT, Dimov SS, Rapid Manufacturing: the Technologies and Applications of Rapid Prototyping and Rapid Tooling, Springer, London (2000)
Zein I, Hutmacher DW, Tan KC, Teoh SH, Biomaterials, 23, 1169 (2002)
Langer R, Tirrell D, Nature, 428, 487 (2004)
Soppimath KS, Aminabhavi TM, Kulkarni AR, J. Control. Release, 70, 1 (2001)
Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, Hollister SJ, Das S, Biomaterials, 26, 4817 (2005)
Hamoudeh M, Diab R, Fessi H, Drug. Dev. Ind. Pharm., 34, 698 (2008)
Krzaczkowska J, Fojud Z, Kozak M, Jurga S, Acta Phys. Pol. A, 108, 187 (2005)

[1] Alexis F, Venkatraman SS, Rath SK, Boey F, J. Control. Release, 98, 67 (2004)

[2] Topol EJ, Textbook of Cardiovascular Medicine, 3rd Edition, Lippincott Williams & Wilkins, Philadelphia, PA (2007)

[3] Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL, Am. Heart. J., 151, 1260 (2006)

[4] Williams DO, Abbott JD, Circulation, 116, 2363 (2007)

[5] Bosiers CCM, Deloose K, Berbist J, Peeters P, Vasc. Health Risk Manag., 4, 553 (2008)

[6] Siablis D, Pantelis K, Karnabatidis D, Kagadis GC, Katsanos K, Tsolakis J, J. Endovasc. Ther., 12, 685 (2005)

[7] Grant AG, White CJ, Collins TJ, Jenkins JS, Reilly JP, Ramee SR, Catherter. Cardiovasc. Interv., 71, 112 (2008)

[8] Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Captuo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, N. Engl. J. Med., 349, 1315 (2003)

[9] Xie J, Wang CH, Pharmaceut. Res., 23, 1817 (2006)

[10] Zeng J, Xu X, Chen X, Liang Q, Bian X, Yang L, Jing X, J. Control. Release, 92, 227 (2003)

[11] Liebmann J, Cook JA, Lipschultz C, Cancer Chemoth. Pharm., 33, 331 (1994)

[12] Wessely R, Eur. Heart. J., 28, 2720 (2007)

[13] Wang TH, Wang HS, Soong YK, Cancer Chemoth. Pharm., 88, 2619 (2000)

[14] Fischell TA, Circulation, 94, 1494 (1996)

[15] Pham DT, Dimov SS, Rapid Manufacturing: the Technologies and Applications of Rapid Prototyping and Rapid Tooling, Springer, London (2000)

[16] Zein I, Hutmacher DW, Tan KC, Teoh SH, Biomaterials, 23, 1169 (2002)

[17] Langer R, Tirrell D, Nature, 428, 487 (2004)

[18] Soppimath KS, Aminabhavi TM, Kulkarni AR, J. Control. Release, 70, 1 (2001)

[19] Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, Hollister SJ, Das S, Biomaterials, 26, 4817 (2005)

[20] Hamoudeh M, Diab R, Fessi H, Drug. Dev. Ind. Pharm., 34, 698 (2008)

[21] Krzaczkowska J, Fojud Z, Kozak M, Jurga S, Acta Phys. Pol. A, 108, 187 (2005)