Synthesis of New pH-Sensitive Amphiphilic Block Copolymers and Study for the Micellization Using a Fluorescence Probe

Kyung Min Kim; Song-yee Choi; Hee Jeong Jeon; Jae Yeol Lee; Dong Joon Choo; Jungahn Kim; Yong Soo Kang; Hyun-Oh Yoo

Macromolecular Research, Vol.16, No.2, 169-177, February, 2008

Kyung Min Kim, Song-yee Choi, Hee Jeong Jeon, Jae Yeol Lee, Dong Joon Choo , Jungahn Kim^†, Yong Soo Kang¹, and Hyun-Oh Yoo¹

Department of Chemistry, Kyunghee University, Seoul 130-701, Korea
¹Department of Chemical Engineering, Hanyang University, Seoul 133-791, Korea

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This paper reports a facile synthesis of new water-soluble poly(ethylene oxide) (PEO)-based amphiphilic block copolymers showing pH sensitive phase transition behaviors. The copolymers were prepared by atom transfer radical polymerization (ATRP) of methacrylamide type of monomers carrying a sulfonamide group using a PEObased macroinitiator and a Cu(I)Br/Me6TREN catalytic system in aqueous media. The resulting polymers were characterized by a combination of 1H-NMR, size exclusion chromatography, and UV/Visible spectrophotometeric analysis. The micellization of the block copolymers as a drug-loading mechanism in aqueous media using fluorescein salt was examined as a function of pH. The stable micelle formation and its loading efficacy suggest that the block copolymers can be used as precursors for drug-nanocontainers.

Keywords:pH-sensitive block copolymer;macroinitiator;atom transfer radical polymerization;sulfonamide groups;micellization;fluorescence probe

[References]

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Park SY, Bae YH, Macromol. Rapid Commun., 20(5), 269 (1999)
Pinto-Alphandary H, Andremont A, Couvreur P, Int. J. Antimicrob. Agents, 13, 155 (2000)
Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B, Proc. Natl. Am. Sci. USA, 100, 6039 (2003)
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Torchilin VP, Colloids Surf. B: Biointerfaces, 16, 305 (1999)
Nishiyama N, Kataoka K, Pharmacol. Therapeutics, 112, 630 (2006)
Nishiyama N, Okazaki S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, Nishio K, Matsumura Y, Kataoka K, Cancer Res., 63, 8977 (2003)
Yang L, Alexandridis P, Curr. Opin. Colloid Interface Sci., 5, 132 (2000)
Discher DE, Eisenberg A, Science, 297, 967 (2002)
Savic R, Luo L, Eisenberg A, Maysinger D, Science, 300, 615 (2003)
Kim KH, Kim J, Jo WH, Polymer, 46(9), 2836 (2005)
Matyjaszewski K, Xia JH, Chem. Rev., 101(9), 2921 (2001)
Wang XS, Jackson RA, Armes SP, Macromolecules, 33(2), 255 (2000)
Li J, Eastman A, J. Biol. Chem., 270, 3203 (1995)
Hirano T, Kikuchi K, Urano Y, Higuchi T, Nagano T, J. Am. Chem. Soc., 122(49), 12399 (2000)
Morton M, Fetters LJ, Rubber Chem. Technol., 48, 359 (1975)
Gilman H, Cartledge FK, J. Organomet. Chem., 2, 447 (1964)
Ciampolini M, Nardi N, Inorg. Chem., 5, 41 (1966)
Kim J, Choi SY, Kim KM, Go DH, Jeon HJ, Lee JY, Park HS, Lee CH, Park HM, Macromol. Res., 15(4), 337 (2007)
Hsieh HL, Quirk RP, Anionic Polymerization; Principles and Practical Applications, Marcel Dekker, New York, 1996, Chap. 4, pp. 71-92
Patten TE, Matyjaszewski K, Adv. Mater., 10(12), 901 (1998)
Davis KA, Matyjaszewski K, Adv. Polym. Sci., 159, 1 (2002)
Coessens V, Pintauer T, Matyaszewski K, Prog. Polym. Sci, 26, 337 (2001)
Patten TE, Xia JH, Abernathy T, Matyjaszewski K, Science, 272(5263), 866 (1996)
Qiu J, Charleux B, Matyaszewski K, Prog. Polym. Sci, 26, 2083 (2001)

[Referenced By]

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[1] Kwon IC, Bae YH, Kim SW, Nature, 354, 291 (1991)

[2] Prokop, Kozlov E, Carlesso G, Davidson JM, Adv. Polym. Sci., 160, 119 (2002)

[3] Hoffmann AS, in Controlled Drug Delivery: Challenges and Strategies, K. N. Park, Ed., Am. Chem. Soc., Washington, D. C., 1997, Chap. 24, pp. 485-498

[4] Hu ZB, Chen YY, Wang CJ, Zheng YD, Li Y, Nature, 393(6681), 149 (1998)

[5] Chen GH, Hoffman AS, Nature, 373(6509), 49 (1995)

[6] Dong LC, Hoffman AS, J. Control. Release, 15, 141 (1991)

[7] Ringsdorf H, J. Polym. Sci., Symp., No. 51, 135 (1975)

[8] Hofmann V, Przybylski M, Ringsdorf H, Ritter H, Makromol. Chem., 177, 1791 (1976)

[9] Abel G, Connors TA, Ross WCJ, Nam NH, Hoellinger H, Pichat L, Eur. J. Cancer, 9, 49 (1973)

[10] Supuran CT, Casini A, Scozzafava A, Med. Res. Rev., 23, 535 (2003)

[11] Spinks CA, Wyatt GM, Lee HA, Morgan MRA, Bioconjugate Chem., 10, 583 (1999)

[12] Park SY, Bae YH, Macromol. Rapid Commun., 20(5), 269 (1999)

[13] Pinto-Alphandary H, Andremont A, Couvreur P, Int. J. Antimicrob. Agents, 13, 155 (2000)

[14] Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B, Proc. Natl. Am. Sci. USA, 100, 6039 (2003)

[15] Jones MC, Leroux JC, Eur. J. Pharm. Biopharm., 48, 101 (1999)

[16] Torchilin VP, Colloids Surf. B: Biointerfaces, 16, 305 (1999)

[17] Nishiyama N, Kataoka K, Pharmacol. Therapeutics, 112, 630 (2006)

[18] Nishiyama N, Okazaki S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, Nishio K, Matsumura Y, Kataoka K, Cancer Res., 63, 8977 (2003)

[19] Yang L, Alexandridis P, Curr. Opin. Colloid Interface Sci., 5, 132 (2000)

[20] Discher DE, Eisenberg A, Science, 297, 967 (2002)

[21] Savic R, Luo L, Eisenberg A, Maysinger D, Science, 300, 615 (2003)

[22] Kim KH, Kim J, Jo WH, Polymer, 46(9), 2836 (2005)

[23] Matyjaszewski K, Xia JH, Chem. Rev., 101(9), 2921 (2001)

[24] Wang XS, Jackson RA, Armes SP, Macromolecules, 33(2), 255 (2000)

[25] Li J, Eastman A, J. Biol. Chem., 270, 3203 (1995)

[26] Hirano T, Kikuchi K, Urano Y, Higuchi T, Nagano T, J. Am. Chem. Soc., 122(49), 12399 (2000)

[27] Morton M, Fetters LJ, Rubber Chem. Technol., 48, 359 (1975)

[28] Gilman H, Cartledge FK, J. Organomet. Chem., 2, 447 (1964)

[29] Ciampolini M, Nardi N, Inorg. Chem., 5, 41 (1966)

[30] Kim J, Choi SY, Kim KM, Go DH, Jeon HJ, Lee JY, Park HS, Lee CH, Park HM, Macromol. Res., 15(4), 337 (2007)

[31] Hsieh HL, Quirk RP, Anionic Polymerization; Principles and Practical Applications, Marcel Dekker, New York, 1996, Chap. 4, pp. 71-92

[32] Patten TE, Matyjaszewski K, Adv. Mater., 10(12), 901 (1998)

[33] Davis KA, Matyjaszewski K, Adv. Polym. Sci., 159, 1 (2002)

[34] Coessens V, Pintauer T, Matyaszewski K, Prog. Polym. Sci, 26, 337 (2001)

[35] Patten TE, Xia JH, Abernathy T, Matyjaszewski K, Science, 272(5263), 866 (1996)

[36] Qiu J, Charleux B, Matyaszewski K, Prog. Polym. Sci, 26, 2083 (2001)