Skip to main content
SpringerLink
Log in

Control of Drug Loading and Release Properties of Spider Silk Sub-Microparticles

  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

The controlled delivery of water-soluble substances is one important issue in pharmaceutical and medical applications. Biocompatible polymers which can easily be processed in an all aqueous process with controllable and adjustable properties have been thoroughly investigated in the past for their use as drug delivery vehicles. Recently, we established sub-microparticles produced from the engineered spider silk protein eADF4(C16) as potential carriers for highly water-soluble drugs. Here, we investigate the influence of crosslinking on the structural integrity of the sub-microparticles and the effect on drug loading and release. To analyze the order-of-addition influences of processing of sub-microparticles on drug loading and release, we tested five different preparation routes. We showed that the preparation route largely influences the loading capacity of the eADF4(C16) sub-microparticles. In the preferred preparation route, rhodamine B and the protein are co-precipitated by salting-out, yielding the highest loading. Further, crosslinking the proteins with APS (ammonium persulfate) and Rubpy (Tris(2,2′- bipyridyl)dichlororuthenium(II)) has an impact on loading as well as on the release behavior of drug molecules as shown exemplarily with rhodamine B.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Langer, R. (1990). New methods of drug delivery. Science, 249(4976), 1527–1533.

    Article  Google Scholar 

  2. Langer, R., & Peppas, N. A. (2003). Advances in biomaterials, drug delivery, and bionanotechnology. AICHE Journal, 49(12), 2990–3006.

    Article  Google Scholar 

  3. Choy, Y. B., Cheng, F., Choi, H., Kim, K. K. (2008). Monodisperse gelatin microspheres as a drug delivery vehicle: Release profile and effect of crosslinking density. Macromolecular Bioscience, 8(8), 758–765.

    Article  Google Scholar 

  4. Berkland, C., Kim, K., Pack, D. W. (2001). Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions. Journal of Controlled Release, 73(1), 59–74.

    Article  Google Scholar 

  5. Herrmann, J., & Bodmeier, R. (1995). The effect of particle microstructure on the somatostatin release from poly(lactide) microspheres prepared by a W/O/W solvent evaporation method. Journal of Controlled Release, 36(1–2), 63–71.

    Article  Google Scholar 

  6. Wenk, E., Wandrey, A. J., Merkle, H. P., Meinel, L. (2008). Silk fibroin spheres as a platform for controlled drug delivery. Journal of Controlled Release, 132(1), 26–34.

    Article  Google Scholar 

  7. Hofmann, S., Foo, C. T., Rossetti, F., Textor, M., Vunjak-Novakovic, G., Kaplan, D. L., et al. (2006). Silk fibroin as an organic polymer for controlled drug delivery. Journal of Controlled Release, 111(1–2), 219–227.

    Article  Google Scholar 

  8. Freiberg, S., & Zhu, X. X. (2004). Polymer microspheres for controlled drug release. International Journal of Pharmaceutics, 282(1–2), 1–18.

    Article  Google Scholar 

  9. Lammel, A., Schwab, M., Hofer, M., Winter, G., Scheibel, T. (2011). Recombinant spider silk particles as drug delivery vehicles. Biomaterials, 32(8), 2233–2240.

    Article  Google Scholar 

  10. Lammel, A., Schwab, M., Slotta, U., Winter, G., Scheibel, T. (2008). Processing conditions for the formation of spider silk microspheres. ChemSusChem, 1(5), 413–416.

    Article  Google Scholar 

  11. Spiess, K., Lammel, A., Scheibel, T. (2010). Recombinant spider silk proteins for applications in biomaterials. Macromolecular Bioscience, 10(9), 998–1007.

    Article  Google Scholar 

  12. Liebmann, B., Huemmerich, D., Scheibel, T., Fehr, M. (2008). Formulation of poorly water-soluble substances using self-assembling spider silk protein. Colloid Surface A, 331(1–2), 126–132.

    Article  Google Scholar 

  13. Huemmerich, D., Helsen, C. W., Quedzuweit, S., Oschmann, J., Rudolph, R., Scheibel, T. (2004). Primary structure elements of spider dragline silks and their contribution to protein solubility. Biochemistry-Us, 43(42), 13604–13612.

    Article  Google Scholar 

  14. Slotta, U. K., Rammensee, S., Gorb, S., Scheibel, T. (2008). An engineered spider silk protein forms microspheres. Angewandte Chemie International Edition, 47(24), 4592–4594.

    Article  Google Scholar 

  15. Schacht, K., & Scheibel, T. (2011). Controlled hydrogel formation of a recombinant spider silk protein. Biomacromolecules, 12(7), 2488–2495.

    Article  Google Scholar 

  16. Hardy, J. G., Romer, L. M., Scheibel, T. R. (2008). Polymeric materials based on silk proteins. Polymer, 49(20), 4309–4327.

    Article  Google Scholar 

  17. Rammensee, S., Huemmerich, D., Hermanson, K. D., Scheibel, T., Bausch, A. R. (2006). Rheological characterization of hydrogels formed by recombinantly produced spider silk. Applied Physics A: Materials, 82(2), 261–264.

    Article  Google Scholar 

  18. Slotta, U., Tammer, M., Kremer, F., Koelsch, P., Scheibel, T. (2006). Structural analysis of spider silk films. Supramolecular Chemistry, 18(5), 465–471.

    Article  Google Scholar 

  19. Hermanson, K. D., Harasim, M. B., Scheibel, T., Bausch, A. R. (2007). Permeability of silk microcapsules made by the interfacial adsorption of protein. Physical Chemistry Chemical Physics, 9(48), 6442–6446.

    Article  Google Scholar 

  20. Hermanson, K. D., Huemmerich, D., Scheibel, T., Bausch, A. R. (2007). Engineered microcapsules fabricated from reconstituted spider silk. Advanced Materials, 19(14), 1810–1815.

    Article  Google Scholar 

  21. Spiess, K., Ene, R., Keenan, C. D., Senker, J., Kremer, F., Scheibel, T. (2011). Impact of initial solvent on thermal stability and mechanical properties of recombinant spider silk films. Journal of Materials Chemistry, 21(35), 13594–13604.

    Article  Google Scholar 

  22. Leal-Egana, A., & Scheibel, T. (2010). Silk-based materials for biomedical applications. Biotechnology and Applied Biochemistry, 55, 155–167.

    Article  Google Scholar 

  23. Lammel, A. S., Hu, X., Park, S. H., Kaplan, D. L., Scheibel, T. R. (2010). Controlling silk fibroin particle features for drug delivery. Biomaterials, 31(16), 4583–4591.

    Article  Google Scholar 

  24. Almeria, B., Fahmy, T. M., Gomez, A. (2011). A multiplexed electrospray process for single-step synthesis of stabilized polymer particles for drug delivery. Journal of Controlled Release, 154(2), 203–210.

    Article  Google Scholar 

  25. Park, M. K., Deng, S., Advincula, R. C. (2005). Sustained release control via photo-cross-linking of polyelectrolyte layer-by-layer hollow capsules. Langmuir, 21(12), 5272–5277.

    Article  Google Scholar 

  26. Fancy, D. A., & Kodadek, T. (1999). Chemistry for the analysis of protein-protein interactions: Rapid and efficient cross-linking triggered by long wavelength light. Proceedings of the National Academy of Sciences of the United States of America, 96(11), 6020–6024.

    Article  Google Scholar 

  27. Hunter, R. J. (1981). Zeta potential in colloid science. New York: Academic Press.

    Google Scholar 

  28. Mchedlov-Petrossyan, N. O., Vodolazkaya, N. A., Doroshenko, A. O. (2003). Ionic equilibria of fluorophores in organized solutions: The influence of micellar microenvironment on protolytic and photophysical properties of rhodamine B. Journal of Fluorescence, 13(3), 235–248.

    Article  Google Scholar 

  29. Chao, C. C., Ma, Y. S., Stadtman, E. R. (1997). Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems. Proceedings of the National Academy of Sciences of the United States of America, 94(7), 2969–2974.

    Article  Google Scholar 

  30. Beppu, M. M., Vieira, R. S., Aimoli, C. G., Santana, C. C. (2007). Crosslinking of chitosan membranes using glutaraldehyde: Effect on ion permeability and water absorption. Journal of Membrane Science, 301(1–2), 126–130.

    Article  Google Scholar 

  31. Hofer, M., Winter, G., Myschik, J. (2012). Recombinant spider silk particles for controlled delivery of protein drugs. Biomaterials, 33(5), 1554–1562.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Bundesministerium für Bildung und Forschung (BMBF), grant number 13N11340. We gratefully thank Lukas Eisoldt and Andrew Smith for proof reading and Felix Bauer, Lukas Eisoldt, Anja Hagenau, Andrew Smith, Michael Suhre, and Stefanie Wohlrab for critical comments on the manuscript. We would like to thank Nicolas Helfricht for assistance with the zeta potential measurements.

Author information

Authors and Affiliations

  1. Lehrstuhl Biomaterialien, Fakultät für Angewandte Naturwissenschaften, Universität Bayreuth, Universitätsstr. 30, 95447, Bayreuth, Germany

    Claudia Blüm & Thomas Scheibel

Authors
  1. Claudia Blüm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Scheibel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Scheibel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blüm, C., Scheibel, T. Control of Drug Loading and Release Properties of Spider Silk Sub-Microparticles. BioNanoSci. 2, 67–74 (2012). https://doi.org/10.1007/s12668-012-0036-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12668-012-0036-7

Keywords

Search

Navigation