Skip to main content
Biointerphases

Journal for Biophysical Chemistry

Download PDF

Design, synthesis, and degradation studies of new enzymatically erodible Poly(hydroxyethyl methacrylate)/poly(ethylene oxide) hydrogels

Biointerphases volume 2, pages 131–135 (2007)Cite this article

Abstract

This work describes the synthesis and the study of poly(hydroxyethyl methacrylate) PHEMA hydrogels, cross-linked by poly(ethylene oxide)(PEO) chains containing the Gly-Gly-Leu tripeptide. This sequence was selected for its ability to be cleaved by subtilisin, a bacterial protease. The cross-linker was synthesized by coupling the peptide with two amino-terminated PEO chains of Mw=3400 g/mol. The resulting polymer was characterized by size exclusion chromatography, nuclear magnetic resonance, and mass spectroscopy, and was shown to be readily cleaved by subtilisin. Its esterification of the hydroxyl end groups into methacrylate afforded a macromonomer that was used as a degradable cross-linker and copolymerized with hydroxyethylmethacrylate to form hydrogels. The swelling ratio of the gels increases when the PEO cross-linker/polyHEMA ratio increases. Incubation of these gels with the enzyme led to the total degradation of the gels. These assays show that these gels can be used as drug-delivery systems where the release is triggered by the presence of proteases.

References

  1. N. Peppas, Hydrogels in Medicine and Pharmacy (CRC Press, Boca Raton, FL, 1986).

    Google Scholar 

  2. K. Y. Lee and D. J. Mooney, Chem. Rev. 101, 1869 (2001).

    Article  CAS  Google Scholar 

  3. A. Kishida and Y. Ikada, in Polymeric Biomaterials, 2nd ed., edited by S. Dumitriu (Marcel Dekker, Inc., New York, 2002), p. 133.

    Google Scholar 

  4. D. A. Barrera, E. Zylstra, P. T. Lansbury et al., Macromolecules 28, 425 (1995).

    Article  CAS  Google Scholar 

  5. 5B. Jeong, Y. H. Bae, D. S. Lee, and S. W. Kim, Nature (London) 388, 860 (1997).

    Article  CAS  Google Scholar 

  6. D. K. Han and J. A. Hubbell, Macromolecules 30, 6077 (1997).

    Article  CAS  Google Scholar 

  7. S. J. Bryant and K. S. Anseth, J. Biomed. Mater. Res. 64A, 70 (2003).

    Article  CAS  Google Scholar 

  8. T. Miyata, T. Uragami, and K. Nakamae, Adv. Drug Deliv. Rev. 54, 79 (2002).

    Article  CAS  Google Scholar 

  9. K. Seon Jeong, P. Sang Jun, and I. K. Sun, Smart Mater. Struct. 13, 317 (2004).

    Article  Google Scholar 

  10. K. Naraghi, N. Sahli, M. Belbachir et al., Polym. Int. 51, 912 (2002).

    Article  CAS  Google Scholar 

  11. K. L. Shantha, P. Ravichandran, and K. P. Rao, Biomaterials 16, 1313 (1995).

    Article  CAS  Google Scholar 

  12. H. Brondsted and J. Kopecek, Pharm. Res. 9, 1540 (1992).

    Article  CAS  Google Scholar 

  13. P.-Y. Yeh, P. Kopeckova, and J. Kopecek, Macromol. Chem. Phys. 196, 2183 (1995).

    Article  CAS  Google Scholar 

  14. V. Subr, R. Duncan, and J. Kopecek, J. Biomater. Sci. Polym. Ed. 1, 261 (1990).

    Article  CAS  Google Scholar 

  15. K. Ulbrich, J. Strohalm, and J. Kopecek, Biomaterials 3, 150 (1982).

    Article  CAS  Google Scholar 

  16. J. L. West and J. A. Hubbell, Macromolecules 32, 241 (1999).

    Article  CAS  Google Scholar 

  17. M. P. Lutolf, J. L. Lauer-Fields, H. G. Schmoekel et al., Proc. Natl. Acad. Sci. U.S.A. 100, 5413 (2003).

    Article  CAS  Google Scholar 

  18. A. S. Gobin and J. L. West, FASEB J. 16, 751 (2002).

    CAS  Google Scholar 

  19. N. S. Khelfallah, G. Decher, and P. J. Mésini, Macromol. Rapid Commun. 27, 1004 (2006).

    Article  CAS  Google Scholar 

  20. L. A. Lyublinskaya, S. V. Belyaev, A. Y. Strongin et al., Anal. Biochem. 62, 371 (1974).

    Article  CAS  Google Scholar 

  21. K. Morihara, T. Oka, and H. Tsuzuki, Arch. Biochem. Biophys. 138, 515 (1970).

    Article  CAS  Google Scholar 

  22. Y. Kanaoka, T. Takahashi, H. Nakayama et al., Chem. Pharm. Bull. (Tokyo) 33, 1721 (1985).

    Article  CAS  Google Scholar 

  23. V. A. Davankov and M. P. Tsyurupa, Angew. Makromol. Chem. 91, 121 (1980).

    Google Scholar 

  24. M. P. Tsyurupa, A. I. Andreeva, and V. A. Davankov, Angew. Makromol. Chem. 70, 179 (1978).

    Article  CAS  Google Scholar 

  25. V. A. Davankov, M. P. Tsyurupa, and S. V. Rogozhin, Angew. Makromol. Chem. 53, 19 (1976).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut Charles Sadron CNRS UPR 022, 6 rue Boussingault, 67083, Strasbourg, France

    Nawel S. Khelfallah, Gero Decher & Philippe J. Mésini

Authors
  1. Nawel S. Khelfallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gero Decher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philippe J. Mésini
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khelfallah, N.S., Decher, G. & Mésini, P.J. Design, synthesis, and degradation studies of new enzymatically erodible Poly(hydroxyethyl methacrylate)/poly(ethylene oxide) hydrogels. Biointerphases 2, 131–135 (2007). https://doi.org/10.1116/1.2799034

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1116/1.2799034