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On the Release of Proteins from Degrading Dextran Methacrylate Hydrogels and the Correlation with the Rheologic Properties of the Hydrogels

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Abstract

Purpose. To study the release of macromolecules of different sizes (bovine serum albumin, immunoglobulin G) from degrading (addition of dextranase) dextran methacrylate (dex-MA) hydrogels and to correlate the release with the evolution of the rehologic properties of the hydrogels during degradation.

Methods. The size of the macromolecules, the degree of substitution (i.e., number of methacrylates per 100 glycopyranose residues) of the dex-MA and the dextranase concentration in the hydrogels was varied. The rheologic properties were measured with a controlled stress rheometer.

Results. The release from dex-MA hydrogels without dextranase was very small [7-20% (time frame up to 180 days)] showing that most of the molecules were entrapped within the hydrogel network. The release from degrading dex-MA hydrogels followed zero-order kinetics for all molecules during a substantial period of the release. This was explained by a liberation and an increasing diffusivity of the proteins in the course of the degradation. The total amount released and the release rates could be well correlated with the rheologically observed degradation rates.

Conclusions. It was shown that rheology can be a useful tool to help explain the release from degrading hydrogels.

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REFERENCES

  1. N. Vyavahare and J. Kohn. Photocrosslinked hydrogels based on copolymers of poly(ethylene glycol) and lysine. J. Polymer Sci. 32:1271-1281 (1994).

    Google Scholar 

  2. B. Amsden. Solute diffusion within hydrogels: mechanisms and models. Macromolecules 31:8382-8395 (1998).

    Google Scholar 

  3. B. Amsden. An obstruction-scaling model for diffusion in homogeneous hydrogels. Macromolecules 32:874-879 (1999).

    Google Scholar 

  4. S. Lu and K. S. Anseth. Release behavior of high molecular weight solutes from poly(ethylene glycol)-based degradable networks. Macromolecules 33:2509-2515 (2000).

    Google Scholar 

  5. W. E. Hennink, O. Franssen, W. N. E. Van Dijk-Wolthuis, and H. Talsma. Dextran hydrogels for the controlled release of proteins. J. Control. Release 44:107-114 (1997).

    Google Scholar 

  6. O. Franssen, O. P. Vos, and W. E. Hennink. Delayed release of a model protein from enzymatically degrading dextran hydrogels. J. Control. Release 44:237-245 (1997).

    Google Scholar 

  7. W. N. E. Van Dijk-Wolthuis, O. Franssen, H. Talsma, M. J. Van Steenbergen, J. J. Kettenes-Van Den Bosch, and W. E. Hennink. Synthesis, characterization and polymerization of glycidyl methacrylate derivatized dextran. Macromolecules 28:6317-6322 (1995).

    Google Scholar 

  8. W. N. E. Van Dijk-Wolthuis, J. J. Kettenes-Van Den Bosch, A. Van der Kerk-Van Hoof, and W. E. Hennink. Reaction of dextran with glycidyl methacrylate: an unexpected transesterification. Macromolecules 30:3411-3414 (1997).

    Google Scholar 

  9. W. E. Hennink, H. Talsma, J. C. H. Borchert, S. C. DeSmedt, and J. Demeester. Controlled release of proteins from dextran hydrogels. J. Control. Release 39:47-55 (1995).

    Google Scholar 

  10. M. Bradford. A rapid and sensitive method for the quantification of microgram quantities of protein using the principle of protein-dye binding. Anal. Biochem. 72:248-254 (1976).

    Google Scholar 

  11. T. K. L. Meyvis, S. C. DeSmedt, W. E. Hennink, and J. Demeester. Rheological monitoring of long-term degrading hydrogels. J. Rheol. 43:933-950 (1999).

    Google Scholar 

  12. S.-H. Kim and C.-C. Chu. Pore structure analysis of swollen dextran methacrylate hydrogels by SEM and mercury intrusion porosismetry. J. Biomed. Mater. Res. 53:258-266 (2000).

    Google Scholar 

  13. W.-Y. Kuu, R. W. Wood, and T. J. Roseman. Factors influencing the kinetics of solute release. In A. Kydonieus (ed.), Treatise on Controlled Drug Delivery, Marcel Dekker, New York, 1992 pp. 37-154.

    Google Scholar 

  14. N. J. Chang and K. J. Himmelstein. Dissolution-diffusion controlled constant-rate release from heterogeneously loaded drug-containing materials. J. Control. Release 12:201-212 (1990).

    Google Scholar 

  15. W. N. E. Van Dijk-Wolthuis, S. K. Y. Tsang, M. J. Van Steenbergen, C. Hoogeboom, and W. E. Hennink. Degradation and release behaviour of dextran based hydrogels. Macromolecules 30:4639-4645 (1997).

    Google Scholar 

  16. S. C. De Smedt, T. K. L. Meyvis, J. Demeester, P. Van Oostveldt, J. C. G. Blonk, and W. E. Hennink. Diffusion of macromolecules in dextran methacrylate solutions and gels as studied by confocal scanning laser microscopy. Macromolecules 30:4863-4870 (1997).

    Google Scholar 

  17. O. Franssen, R. D. Van Rooijen, D. DeBoer, R. A. A. Maes, and W. E. Hennink. Enzymatic degradation of crosslinked dextrans. Macromolecules 32:2896-2902 (1999).

    Google Scholar 

  18. J. D. Ferry. Viscoelastic Properties of Polymers, John Wiley & Sons, New York, 1980.

    Google Scholar 

  19. T. K. L. Meyvis, S. C. De Smedt, W. E. Hennink, and J. Demeester. Influence of the degradation mechanism of hydrogels on their elastic and swelling properties during degradation. Macromolecules 33:4717-4725 (2000).

    Google Scholar 

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Meyvis, T., De Smedt, S., Stubbe, B. et al. On the Release of Proteins from Degrading Dextran Methacrylate Hydrogels and the Correlation with the Rheologic Properties of the Hydrogels. Pharm Res 18, 1593–1599 (2001). https://doi.org/10.1023/A:1013038716373

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  • DOI: https://doi.org/10.1023/A:1013038716373

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