약물전달체로서 디옥시콜산이 결합된 히알루론산의 제조와 특성

최창용; 박준규; 김원석; 장미경; 나재운; Changyong Choi; Jun-Kyu Park; Won Suk Kim; Mi-Kyeong Jang; Jae-Woon Nah

Polymer(Korea), Vol.35, No.2, 119-123, March, 2011

Export Citation

약물전달체로서 디옥시콜산이 결합된 히알루론산의 제조와 특성

Preparation and Characterization of Deoxycholic Acid-Grafted Hyaluronic Acid as a Durg Carrier

최창용 , 박준규, 김원석, 장미경 ^†, 나재운 ^†

순천대학교 공과대학 고분자공학과

Changyong Choi , Jun-Kyu Park, Won Suk Kim, Mi-Kyeong Jang^†, and Jae-Woon Nah^†

Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 540-742, Korea

E-mail:,

초록

본 연구에서는 항암제 전달체로 응용하기 위하여 천연고분자인 히알루론산(hyaluronic acid, HA)에 소수성기 도입을 위하여 담즙산(bile acid) 중 하나인 디옥시콜산(deoxycholic acid)(DA)을 개질하여 양친성 공중합체를 제조하였고, 이를 항암제 전달체로 응용하고자 하였다. 디옥시콜산이 결합된 히알루론산(HADA)의 물리화학적 특성은 1H NMR, FTIR, spectrophotometer와 TEM을 이용하여 측정하였다. 디옥시콜산이 결합된 히알루론산에 항암제(파클리탁셀)를 투석방법을 통하여 봉입시켰고, in vitro에서 KB 세포에 대한 항암활성을 확인하였다. 제조된 디옥시콜산이 결합된 히알루론산이 항암제 전달체로서의 응용 가능성을 제시하였다.

To develop hyaluronic acid (HA)-based anticancer agent carrier, hyaluronic acid was chemically modified with the hydrophobic group of deoxycholic acid(DA). The physicochemical properties of the deoxycholic acid-conjugated HA (HADA) were investigated by using 1H NMR, FTIR, spectrophotometer and TEM. Paclitaxel (Tx)-loaded HADA nanoparticles were prepared by a dialysis method. The loading efficiency of drug and drug contents of Tx-loaded HADA nanoparticles (HADA-Tx) were measured by HPLC. The anticancer activity of HADA-Tx was investigated by its cytotoxicity against KB cell in vitro. The HADA-Tx was shown to have the superior potential for the anticancer drug delivery.

Keywords:hyaluronic acid;bile acid;deoxycholic acid;drug carrier;nanoparticle.

[References]

Wu XY, Lee PI, J. Appl. Polym. Sci., 77(4), 833 (2000)
Laurent TC, Wenner-Gren International Series., Portland Press, London, Vol 72 (1998)
Prestwitch GD, Marecak DM, Marecek JF, J. Control.Release., 53, 93 (1998)
Luo Y, Kirker KR, Prestwich GD, J. Control. Release., 69, 169 (2000)
Park SN, Lee HJ, Suh H, Biomaterials., 22, 1205 (2002)
Park SN, Lee HJ, Suh H, Biomaterials., 24, 1631 (2003)
Nam HS, Kim JH, An JH, Chung DJ, Polym.(Korea), 25(4), 476 (2001)
Hunt JA, Joshi HN, Stella VJ, Topp EM, J.Control. Release., 12, 159 (1990)
Benedetti L, Cortivo R, Berti T, Pea F, Marzzo M, Moras M, Abatangel G, Biomaterials., 14, 1154 (1993)
Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naurnann A, J. Biomed. Mater. Res., 42, 172 (1998)
Chen GP, Ito Y, Imanishi Y, Magnani A, Lamponi S, Barbucci R, Bioconjugate Chem., 8, 730 (1997)
Hahn SK, Oh EJ, Miyamoto H, Shimbouji T, Int. J.Pharm., 322, 44 (2006)
Hahn SK, Park JK, Tomimatsu T, Shimbouji T, Int. J. Bio. Macromol., 40, 374 (2007)
Ko YK, Kim SH, Jeong JS, Park JS, Lim JY, Kim MS, Lee HB, Khang G, Polym.(Korea), 31(6), 505 (2007)
Kim SJ, Hahn SK, Kim MJ, Kim DH, Lee YP, J. Control. Release., 104, 323 (2005)
Luo Y, Kirker KR, Prestwich GD, J. Control. Release., 69, 169 (2000)
Oh EJ, Kim JS, Hahn SK, Key Engineering Materials., 342, 525 (2007)
Palumbo P, Pitarresi G, Mandracchia D, Tripodo G, Giammona G, Carbohyd. Polym., 66, 379 (2006)
Agellon B, Torchia EC, Biochim. Biophy., 1386, 198 (2000)
Hong IR, Kim YJ, Polym.(Korea), 32(6), 561 (2008)
Chang Y, Lee SC, Kim KT, Reeves SD, Allcock HR, Macromolecules., 20, 1331 (1987)
Binana-Limbele W, Zana R, Macromolecules., 20, 1331 (1987)
Magny B, Iliopoulos I, Zana R, Audebert R, Langmuir, 10(9), 3180 (1994)

[Referenced By]

[Related Articles]

[1] Wu XY, Lee PI, J. Appl. Polym. Sci., 77(4), 833 (2000)

[2] Laurent TC, Wenner-Gren International Series., Portland Press, London, Vol 72 (1998)

[3] Prestwitch GD, Marecak DM, Marecek JF, J. Control.Release., 53, 93 (1998)

[4] Luo Y, Kirker KR, Prestwich GD, J. Control. Release., 69, 169 (2000)

[5] Park SN, Lee HJ, Suh H, Biomaterials., 22, 1205 (2002)

[6] Park SN, Lee HJ, Suh H, Biomaterials., 24, 1631 (2003)

[7] Nam HS, Kim JH, An JH, Chung DJ, Polym.(Korea), 25(4), 476 (2001)

[8] Hunt JA, Joshi HN, Stella VJ, Topp EM, J.Control. Release., 12, 159 (1990)

[9] Benedetti L, Cortivo R, Berti T, Pea F, Marzzo M, Moras M, Abatangel G, Biomaterials., 14, 1154 (1993)

[10] Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naurnann A, J. Biomed. Mater. Res., 42, 172 (1998)

[11] Chen GP, Ito Y, Imanishi Y, Magnani A, Lamponi S, Barbucci R, Bioconjugate Chem., 8, 730 (1997)

[12] Hahn SK, Oh EJ, Miyamoto H, Shimbouji T, Int. J.Pharm., 322, 44 (2006)

[13] Hahn SK, Park JK, Tomimatsu T, Shimbouji T, Int. J. Bio. Macromol., 40, 374 (2007)

[14] Ko YK, Kim SH, Jeong JS, Park JS, Lim JY, Kim MS, Lee HB, Khang G, Polym.(Korea), 31(6), 505 (2007)

[15] Kim SJ, Hahn SK, Kim MJ, Kim DH, Lee YP, J. Control. Release., 104, 323 (2005)

[16] Luo Y, Kirker KR, Prestwich GD, J. Control. Release., 69, 169 (2000)

[17] Oh EJ, Kim JS, Hahn SK, Key Engineering Materials., 342, 525 (2007)

[18] Palumbo P, Pitarresi G, Mandracchia D, Tripodo G, Giammona G, Carbohyd. Polym., 66, 379 (2006)

[19] Agellon B, Torchia EC, Biochim. Biophy., 1386, 198 (2000)

[20] Hong IR, Kim YJ, Polym.(Korea), 32(6), 561 (2008)

[21] Chang Y, Lee SC, Kim KT, Reeves SD, Allcock HR, Macromolecules., 20, 1331 (1987)

[22] Binana-Limbele W, Zana R, Macromolecules., 20, 1331 (1987)

[23] Magny B, Iliopoulos I, Zana R, Audebert R, Langmuir, 10(9), 3180 (1994)