약물방출 스텐트용 생분해성 고분자 필름으로부터 파크리탁셀의 조절 방출

김시은; 이봉수; 김진향; 박귀덕; 한동근; Si Eun Kim; Bong Soo Lee; Jin Hyang Kim; Kwideok Park; Dong Keun Han

Polymer(Korea), Vol.34, No.2, 172-177, March, 2010

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약물방출 스텐트용 생분해성 고분자 필름으로부터 파크리탁셀의 조절 방출

Controlled Release of Paclitaxel from Biodegradable Polymer Films for Drug-Eluting Stents

김시은, 이봉수, 김진향, 박귀덕 , 한동근 ^†

한국과학기술연구원 바이오소재센터

Si Eun Kim, Bong Soo Lee, Jin Hyang Kim, Kwideok Park , and Dong Keun Han^†

Biomaterials Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea

E-mail:

초록

최근 20년간 다양한 세포에서 파크리탁셀(PTX)의 효과에 관한 연구는 많이 있지만, 세포증식을 억제하기 위한 약물방출 동역학에 관한 연구는 거의 보고되지 않고 있다. 본 연구에서는 약물방출스텐트 (DES)에 적용하기 위해서 생분해성 고분자로부터 파크리탁셀의 방출거동을 고찰하였다. 다양한 생분해성 고분자인 poly(lactic acid-co-glycolic acid) (PLGA), poly-L-lactide(PLLA) 및 polycaprolactone(PCL)에 파크리탁셀의 함유량을 달리하여 필름을 제조한 후 약물방출 거동을 평가하였다. 약물방출은 8주 동안 이루어졌으며 FE-SEM을 통해 고분자의 분해정도를 관찰하였다. PCL의 생분해 속도는 가장 느리지만 파크리탁셀의 함량이 같을 경우 PCL로부터의 파크리탁셀 방출속도가 가장 빨랐으며 PLGA 그리고 PLLA 순서를 보였다. 이와 같은 결과를 바탕으로 PCL과 같이 유리전이온도(Tg)가 낮은 고분자의 경우 체내에서 파크리탁셀과 같은 소수성 약물의 움직임이 용이하기 때문에 약물방출 속도가 빠를 수 있음을 제시하고 있다.

Although many researchers have studied the efficacy of paclitaxel (PTX) on many cells during the last two decades, little work has been reported on the importance of release kinetics inhibiting cell proliferation. The aim of this study is to examine the release behavior of the PTX on various biodegradable polymers such as poly(lactic-co-glycolic acid)(PLGA), poly-L-lactide (PLLA), and polycaprolactone (PCL) for drug-eluting stents (DES). The PTX from the fabricated films was released for 8 weeks and the degree of degradation of the films was observed by FE-SEM. Although the degradation time of PCL was the slowest, the PTX release rate was the fastest among them and followed by PLGA and PLLA with the equivalent PTX concentration. It suggests that hydrophobic drug such as PTX from polymer with low Tg like PCL could be moved easily and released rapidly in body temperature.

Keywords:drug-eluting stents (DES);biodegradable polymer;paclitaxel (PTX);controlled release;degradation

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[2] Kang E, Wang H, Kwon IK, Anal. Chem., 78, 8036 (2006)

[3] Hiatt BL, Ikeno F, Yeung AC, Catheter. Cardiovasc. Interv., 55, 409 (2002)

[4] Stone GW, Ellis SG, Cox DA, Circulation, 109, 1942 (2004)

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

[6] Frank A, Rath SK, Venkatraman SS, J. Control. Rel., 102, 333 (2005)

[7] Seung KB, Kor. Circul. J., 33, 857 (2003)

[8] Winzenburg G, Schmidt C, Fuchs S, Adv. Drug. Deliv. Rev., 56, 1453 (2004)

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

[10] Wang TH, Wang HS, Soong YK, Cancer, 88, 2619 (2000)

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

[12] Danhire F, Lecouturier N, Vroman B, J. Control. Rel., 133, 11 (2009)

[13] Lao LL, Venkatraman SS, J. Control. Rel., 130, 9 (2008)

[14] Serruys P, Sianos G, Abizaid A, J. Am. Coll. Cardiol., 46, 253 (2005)

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

[16] Liggins RT, Burt HM, Int. J. Pharm., 282, 61 (2004)

[17] Jacksona JK, Smitha J, Letchford K, Int. J. Pharm., 283, 97 (2004)

[18] Jadhav NR, Gaikwad VL, Nair KJ, Asian J. Pharm., 3, 82 (2009)

[19] Westedt U, Wittmar M, Hellwig M, J. Control. Rel., 111, 235 (2006)

[20] Shi R, Burt HM, Int. J. Pharm., 271, 167 (2004)

[21] Ooya T, Lee J, Park K, J. Control. Rel., 93, 121 (2003)