pH-Induced Micellization of Biodegradable Block Copolymers Containing Sulfamethazine

Woo Sun Shim; Jae Sung Lee; Doo Sung Lee

Macromolecular Research, Vol.13, No.4, 344-351, August, 2005

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pH-Induced Micellization of Biodegradable Block Copolymers Containing Sulfamethazine

Woo Sun Shim, Jae Sung Lee, and Doo Sung Lee^†

Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Korea

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pH-sensitive block copolymers were synthesized by coupling reaction of sulfamethazine and amphiphilic diblock copolymer, and their micellization-demicellization behavior was investigated. Sulfamethazine (SM), a derivative of sulfonamide, was introduced as a pH responsive moiety while methoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PDLLA) and methoxy poly(ethylene glycol)-poly(D,L-lactide-co-ε-caprolactone) (MPEG-PCLA) were used as biodegradable amphiphilic diblock copolymers. After the sulfamethazine was carboxylated by the reaction with succinic anhydride, the diblock copolymer was conjugated with sulfamethazine by coupling reaction in the presence of DCC. The critical micelle concentration (CMC) and mean diameter of the micelles were examined at various pH conditions through fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. For MPEG-PDLLA-SM and MPEG-PCLA-SM solutions, the pH-dependent micellization-demicellization was achieved within a narrow pH band, which was not observed in the MPEG-PDLLA and MPEG-PCLA solutions. The micelle showed a spherical morphology and had a very narrow size distribution. This pH-sensitive block copolymer shows potential as a site-targeted drug carrier.

Keywords:pH-sensitive;sulfamethazine;micelle-demicelle transition;block copolymer

[References]

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Soma CE, Dubernet C, Barratt G, Nemati F, Appel M, Benita S, Couvreur P, Pharm. Res., 16, 1710 (1999)
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Jeong B, Bae YH, Lee DS, Kim SW, Nature, 338, 860 (1997)
Soppimath KS, Kulkarni AR, Aminabhavi TM, J. Control. Release, 75, 331 (2001)
Torres-Lugo M, Peppas NA, Macromolecules, 32(20), 6646 (1999)
Yao L, Krause S, Macromolecules, 36(6), 2055 (2003)
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Murthy N, Robichaud JR, Tirrell DA, Stayton PS, Hoffman AS, J. Control. Release, 61, 137 (1999)
Lee AS, Butun V, Vamvakaki M, Armes SP, Pople JA, Gast AP, Macromolecules, 35(22), 8540 (2002)
Gohy JF, Lohmeijer BGG, Varshney SK, Decamps B, Leroy E, Boileau S, Schubert US, Macromolecules, 35(26), 9748 (2002)
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Shim WS, Lee DS, J. Control. Release, submitted.

[Referenced By]

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[1] Tobio M, Gref R, Sanchez A, Langer R, Alonso MJ, Pharm. Res., 15, 270 (1998)

[2] Soma CE, Dubernet C, Barratt G, Nemati F, Appel M, Benita S, Couvreur P, Pharm. Res., 16, 1710 (1999)

[3] Cammas S, Suzuki K, Sone C, Sakurai Y, Kataoka K, Okano T, J. Control. Release, 48, 157 (1997)

[4] Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y, J. Control. Release, 24, 119 (1993)

[5] Kataoka K, J. Macromol. Sci.-Pure Appl. Chem., A31, 1759 (1994)

[6] Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K, Inoue S, J. Control. Release, 11, 269 (1990)

[7] Ding Z, Long CJ, Hayashi Y, Bulmus EV, Hoffman AS, Stayton PS, Bioconjugate Chem., 10, 395 (1999)

[8] Jeong B, Bae YH, Lee DS, Kim SW, Nature, 338, 860 (1997)

[9] Soppimath KS, Kulkarni AR, Aminabhavi TM, J. Control. Release, 75, 331 (2001)

[10] Torres-Lugo M, Peppas NA, Macromolecules, 32(20), 6646 (1999)

[11] Yao L, Krause S, Macromolecules, 36(6), 2055 (2003)

[12] Filipcsei G, Feher J, Zrinyi M, J. Mol. Struct., 554, 109 (2000)

[13] Stubbs M, McSheehy PM, Griffiths JR, Bashford CL, Mol. Med. Today, 6, 15 (2000)

[14] Tannock IF, Rotin D, Cancer Res., 49, 4373 (1989)

[15] Tonge SR, Tighe BJ, Adv. Drug Deliv. Rev., 53, 109 (2001)

[16] Murthy N, Robichaud JR, Tirrell DA, Stayton PS, Hoffman AS, J. Control. Release, 61, 137 (1999)

[17] Lee AS, Butun V, Vamvakaki M, Armes SP, Pople JA, Gast AP, Macromolecules, 35(22), 8540 (2002)

[18] Gohy JF, Lohmeijer BGG, Varshney SK, Decamps B, Leroy E, Boileau S, Schubert US, Macromolecules, 35(26), 9748 (2002)

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

[20] Kang SI, Bae YH, J. Control. Release, 80, 145 (2002)

[21] Kalyanasundaram K, Thomas JK, J. Am. Chem. Soc., 99, 2039 (1977)

[22] Shim WS, Lee DS, J. Control. Release, submitted.