Methotrexate-Incorporated Polymeric Micelles Composed of Methoxy Poly(ethylene glycol)-Grafted Chitosan

Young-Il Jeong; Dong-Hyuk Seo; Don-Gon Kim; Changyong Choi; Mi-Kyeong Jang; Jae-Woon Nah; Yoonkyung Park

Macromolecular Research, Vol.17, No.7, 538-543, July, 2009

Export Citation

Methotrexate-Incorporated Polymeric Micelles Composed of Methoxy Poly(ethylene glycol)-Grafted Chitosan

Young-Il Jeong, Dong-Hyuk Seo, Don-Gon Kim, Changyong Choi , Mi-Kyeong Jang , Jae-Woon Nah^†, and Yoonkyung Park¹

Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 540-742, Korea
¹Department of Biotechnology and BK21 Research Team for Protein Activity Control, Chosun University, Gwangju 501-759, Korea

E-mail:

In this study, methotrexate (MTX)-encapsulated polymeric micelles using methoxy poly(ethylene glycol) (MPEG)-grafted chitosan (ChitoPEG) copolymer were prepared. The MTX-incorporated polymeric micelles of ChitoPEG copolymer has a particle size of around 50-100 nm. In 1H nuclear magnetic resonance (NMR) study, the specific peaks of MTX disappeared in heavy water (D2O) and only the specific peak of MPEG was observed, while all of the peaks were confirmed in dimethyl sulfoxide (DMSO). These results indicated that MTX was complexed with chitosan and then formed an ion complex inner-core of the polymeric micelle in an aqueous environment. The drug contents of the polymeric micelle were around 4~12% and the loading efficiency of MTX in the polymeric micelles was higher than 60% (w/w) for all of the formulations. The cytotoxicity of MTX and MTX-incorporated polymeric micelle against CT26 tumor cells was not significantly changed.

Keywords:methotrexate;polymeric micelle;chitosan;ion complex;MPEG.

[References]

Hirano S, Polym. Int., 48, 732 (1999)
Dang JM, Leong KW, Adv. Drug Del. Rev., 58, 487 (2006)
Thanou M, Verhoef JC, Junginger HE, Adv. Drug Del. Rev., 52, 117 (2001)
Chung TW, Yang J, Akaike T, Cho KY, Nah JW, Kim SI, Cho CS, Biomaterials, 23, 2827 (2002)
Chae SY, Jang MK, Nah JW, J. Control. Release, 102, 383 (2005)
Chae SY, Son S, Lee M, Jang MK, Nah JW, J. Control. Release, 109, 330 (2005)
Calvo P, Remunan-Lopez C, Vila-Jato JL, Alonso MJ, Pharm. Res., 14, 1431 (1997)
Kim DG, Choi C, Jeong YI, Jang MK, Nah JW, Kang SK, Bang MS, Macromol. Res., 14(1), 66 (2006)
Kataoka K, Haradaa A, Nagasaki Y, Adv. Drug Del. Rev., 47, 113 (2001)
Nishiyama N, Kataoka K, Adv. Exp. Med. Biol., 519, 155 (2003)
Kim DG, Jeong YI, Nah JW, J. Appl. Polym. Sci., 105(6), 3246 (2007)
Thunemann AF, Beyermann J, Kukula H, Macromolecules, 33(16), 5906 (2000)
Calabresi P, Parks RE, The Pharmacological Basis of Therapeutics, Macmillan, New York, 1975, p. 1254-1307
Calabresi P, Chabner BA, Goodman LS, Gilman A, Eds., in The Pharmacological Basis of Therapeutics, Macmillan, New York, 1991, p.1243-1247
Li Y, Kwon GS, Pharm. Res., 17, 607 (2000)
Li Y, Kwon GS, Colloid Surface B, 16, 217 (1999)
Kang H, Kim JD, Han SH, Chang IS, J. Control. Release, 81, 135 (2002)
Zhang Y, Zhuo RX, Biomaterials, 26, 2089 (2005)
Nevozhay D, Budzynska R, Kanska U, Jagiello M, Omar MS, Boratynski J, Opolski A, Anticancer Res., 26, 1135 (2006)
Yang X, Zhang Q, Wang Y, Chen H, Zhang H, Gao F, Liu L, Colloid Surface B, 61, 125 (2008)
Mizumura Y, Matsumura Y, Hamaguchi T, Nishiyama N, Kataoka K, Kawaguchi T, Hrushesky WJ, Moriyasu F, Kakizoe T, Jpn. J. Cancer Res., 92, 328 (2001)

[Referenced By]

[Related Articles]

[1] Hirano S, Polym. Int., 48, 732 (1999)

[2] Dang JM, Leong KW, Adv. Drug Del. Rev., 58, 487 (2006)

[3] Thanou M, Verhoef JC, Junginger HE, Adv. Drug Del. Rev., 52, 117 (2001)

[4] Chung TW, Yang J, Akaike T, Cho KY, Nah JW, Kim SI, Cho CS, Biomaterials, 23, 2827 (2002)

[5] Chae SY, Jang MK, Nah JW, J. Control. Release, 102, 383 (2005)

[6] Chae SY, Son S, Lee M, Jang MK, Nah JW, J. Control. Release, 109, 330 (2005)

[7] Calvo P, Remunan-Lopez C, Vila-Jato JL, Alonso MJ, Pharm. Res., 14, 1431 (1997)

[8] Kim DG, Choi C, Jeong YI, Jang MK, Nah JW, Kang SK, Bang MS, Macromol. Res., 14(1), 66 (2006)

[9] Kataoka K, Haradaa A, Nagasaki Y, Adv. Drug Del. Rev., 47, 113 (2001)

[10] Nishiyama N, Kataoka K, Adv. Exp. Med. Biol., 519, 155 (2003)

[11] Kim DG, Jeong YI, Nah JW, J. Appl. Polym. Sci., 105(6), 3246 (2007)

[12] Thunemann AF, Beyermann J, Kukula H, Macromolecules, 33(16), 5906 (2000)

[13] Calabresi P, Parks RE, The Pharmacological Basis of Therapeutics, Macmillan, New York, 1975, p. 1254-1307

[14] Calabresi P, Chabner BA, Goodman LS, Gilman A, Eds., in The Pharmacological Basis of Therapeutics, Macmillan, New York, 1991, p.1243-1247

[15] Li Y, Kwon GS, Pharm. Res., 17, 607 (2000)

[16] Li Y, Kwon GS, Colloid Surface B, 16, 217 (1999)

[17] Kang H, Kim JD, Han SH, Chang IS, J. Control. Release, 81, 135 (2002)

[18] Zhang Y, Zhuo RX, Biomaterials, 26, 2089 (2005)

[19] Nevozhay D, Budzynska R, Kanska U, Jagiello M, Omar MS, Boratynski J, Opolski A, Anticancer Res., 26, 1135 (2006)

[20] Yang X, Zhang Q, Wang Y, Chen H, Zhang H, Gao F, Liu L, Colloid Surface B, 61, 125 (2008)

[21] Mizumura Y, Matsumura Y, Hamaguchi T, Nishiyama N, Kataoka K, Kawaguchi T, Hrushesky WJ, Moriyasu F, Kakizoe T, Jpn. J. Cancer Res., 92, 328 (2001)