pH-Induced Micellization of Biodegradable Block Copolymers Containing Sulfamethazine

  • Shim, Woo-Sun (Department of Polymer Science and Engineering, Sungkyunkwan University) ;
  • Lee, Jae-Sung (Department of Polymer Science and Engineering, Sungkyunkwan University) ;
  • Lee, Doo-Sung (Department of Polymer Science and Engineering, Sungkyunkwan University)
  • Published : 2005.08.31

Abstract

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($D,L-lactide-co-{\varepsilon}-caprolactone$) (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

References

  1. M. Tobio, R. Gref, A. Sanchez, R. Langer, and M. J. Alonso, Pharm. Res., 15, 270 (1998) https://doi.org/10.1023/A:1011922819926
  2. C. E. Soma, C. Dubernet, G. Barratt, F. Nemati, M. Appel, S. Benita, and P. Couvreur, Pharm. Res., 16, 1710 (1999) https://doi.org/10.1023/A:1018902031370
  3. S. Cammas, K. Suzuki, C. Sone, Y. Sakurai, K. Kataoka, and T. Okano, J. Control. Rel., 48, 157 (1997) https://doi.org/10.1016/S0168-3659(97)00040-0
  4. K. Kataoka, G. S. Kwon, M. Yokoyama, T. Okano, and Y. Sakurai, J. Control. Rel., 24, 119 (1993) https://doi.org/10.1016/0168-3659(93)90172-2
  5. K. Kataoka, J. Macromol. Sci. Pure Appl. Chem., A31, 1759 (1994)
  6. M. Yokoyama, M. Miyauchi, N. Yamada, T. Okano, Y. Sakurai, K. Kataoka, and S. Inoue, J. Control. Rel., 11, 269 (1990) https://doi.org/10.1016/0168-3659(90)90139-K
  7. Z. Ding, C. J. Long, Y. Hayashi, E. V. Bulmus, A. S. Hoffman, and P. S. Stayton, Bioconjug. Chem., 10, 395 (1999) https://doi.org/10.1021/bc980108s
  8. B. Jeong, Y. H. Bae, D. S. Lee, and S. W. Kim, Nature, 338, 860 (1997)
  9. K. S. Soppimath, A. R. Kulkarni, and T. M. Aminabhavi, J. Control. Rel., 75, 331 (2001) https://doi.org/10.1016/S0168-3659(01)00358-3
  10. M. Lugo and N. A. Peppas, Macromolecules, 32, 6646 (1999) https://doi.org/10.1021/ma990541c
  11. L. Yao and S. Krause, Macromolecules, 36, 2055 (2003) https://doi.org/10.1021/ma021326q
  12. G. Filipcsei, J. Feher, and M. Zrinyi, J. Mol. Struct., 554, 109 (2000) https://doi.org/10.1016/S0022-2860(00)00564-0
  13. M. Stubbs, P. M. McSheehy, J. R. Griffiths, and C. L. Bashford, Mol. Med. Today, 6, 15 (2000) https://doi.org/10.1016/S1357-4310(99)01615-9
  14. I. F. Tannock and D. Rotin, Cancer Res., 49, 4373 (1989)
  15. S. R. Tonge and B. J. Tighe, Adv. Drug Deliv. Rev., 53, 109 (2001) https://doi.org/10.1016/S0169-409X(01)00236-8
  16. N. Murthy, J. R. Robichaud, D. A. Tirrell, P. S. Stayton, and A. S. Hoffman, J. Control. Rel., 61, 137 (1999) https://doi.org/10.1016/S0168-3659(99)00114-5
  17. A. S. Lee, V. Butun, M. Vamvakaki, S. P. Armes, J. A. Pople, and A. P. Gast, Macromolecules, 35, 8540 (2002) https://doi.org/10.1021/ma011278u
  18. J. Gohy, B. G. G. Lohmeijer, S. K. Varshney, B. Decamps, E. Leroy, S. Boileau, and U. S. Schubert, Macromolecules, 35, 9748 (2002) https://doi.org/10.1021/ma011278u
  19. S. Y. Park and Y. H. Bae, Macromol. Rapid Commun., 20, 269 (1999) https://doi.org/10.1002/(SICI)1521-3927(19990501)20:5<269::AID-MARC269>3.0.CO;2-3
  20. S. I. Kang and Y. H. Bae, J. Control. Rel., 80, 145 (2002) https://doi.org/10.1016/S0168-3659(02)00021-4
  21. K. Kalyanasundaram and J. K. Thomas, J. Am. Chem. Soc., 99, 2039 (1977) https://doi.org/10.1021/ja00449a004
  22. W. S. Shim and D. S. Lee, J. Control. Rel., submitted