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 to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Langer, R. (1990). New methods of drug delivery. Science, 249(4976), 1527–1533.
Langer, R., & Peppas, N. A. (2003). Advances in biomaterials, drug delivery, and bionanotechnology. AICHE Journal, 49(12), 2990–3006.
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.
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.
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.
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.
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.
Freiberg, S., & Zhu, X. X. (2004). Polymer microspheres for controlled drug release. International Journal of Pharmaceutics, 282(1–2), 1–18.
Lammel, A., Schwab, M., Hofer, M., Winter, G., Scheibel, T. (2011). Recombinant spider silk particles as drug delivery vehicles. Biomaterials, 32(8), 2233–2240.
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.
Spiess, K., Lammel, A., Scheibel, T. (2010). Recombinant spider silk proteins for applications in biomaterials. Macromolecular Bioscience, 10(9), 998–1007.
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.
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.
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.
Schacht, K., & Scheibel, T. (2011). Controlled hydrogel formation of a recombinant spider silk protein. Biomacromolecules, 12(7), 2488–2495.
Hardy, J. G., Romer, L. M., Scheibel, T. R. (2008). Polymeric materials based on silk proteins. Polymer, 49(20), 4309–4327.
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.
Slotta, U., Tammer, M., Kremer, F., Koelsch, P., Scheibel, T. (2006). Structural analysis of spider silk films. Supramolecular Chemistry, 18(5), 465–471.
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.
Hermanson, K. D., Huemmerich, D., Scheibel, T., Bausch, A. R. (2007). Engineered microcapsules fabricated from reconstituted spider silk. Advanced Materials, 19(14), 1810–1815.
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.
Leal-Egana, A., & Scheibel, T. (2010). Silk-based materials for biomedical applications. Biotechnology and Applied Biochemistry, 55, 155–167.
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.
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.
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.
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.
Hunter, R. J. (1981). Zeta potential in colloid science. New York: Academic Press.
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.
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.
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.
Hofer, M., Winter, G., Myschik, J. (2012). Recombinant spider silk particles for controlled delivery of protein drugs. Biomaterials, 33(5), 1554–1562.
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.
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
- Drug delivery
- Recombinant spider silk protein