Spider Silk: Structure, Engineering, and Applications - Soft Fibrillar Materials: Fabrication and Applications - page 197

6.4.2
Drug Delivery

The engineered and recombinant spider silk protein eADF has been shown to
be a promising biomaterial for a drug delivery system. The engineered and
recombinantly produced spider silk protein eADF4, which is adopted from the
naturally occurring spider silk protein ADF4 from the European garden spider
Araneus diadematus, represents a more favorable biomaterial [123, 124]. Previous
studies on the assembly process had shown that smooth protein spheres with high
β

-sheet content can be formed by a salting-out process with potassium phosphate
as lyotropic salt avoiding any organic solvent [125, 126]. Lammel et al . described
how the size of eADF4 particles can be easily controlled by the mixing intensity and
the concentrations of potassium phosphate and eADF4 [127]. In order to evaluate
these particles as a drug carrier system, small-molecular-weight drugs were recently
loaded on eADF4 particles [128]. High loading efficiencies of almost 100% could
be achieved with positively charged and sufficiently hydrophobic drug molecules,
and constant release rates were obtained over a period of two weeks.
eADF4 particles were also successfully evaluated as particulate drug carriers for
the delivery of protein drugs [129]. They can be easily prepared in an all-aqueous
process and their colloidal stability is adequate in solutions at neutral pH and low
ionic strength. After preparation, large quantities of lysozyme, as a model protein,
were loaded onto eADF4 particles with almost 100% loading efficiency due to
strong electrostatic interactions between positively charged lysozyme molecules
and negatively charged eADF4 particles. Confocal laser scanning microscopy of
dispersions containing eADF4 particles loaded with FITC-labeled macromolecules
proved that FITC-labeled lysozyme is not only adsorbed to the particles' surface
but also diffuses into the matrix of the eADF4 particles. Lysozyme was released
from eADF4 particles, depending on the pH and ionic strength of the release
medium. Additionally, successful freeze-drying of empty and lysozyme-loaded
eADF4 particles was achieved. No difference between sucrose, trehalose, and
mannitol could be determined when the dried formulations were reconstituted
directly after freeze-drying. With all above advantages, silk protein eADF4 is a
promising drug delivery system, particularly for sensitive drugs like therapeutic
proteins.

6.4.3
Technical Applications

Spider silk has also a potential to be employed in technical applications such
as micromechanical and electronic set-ups. Recombinant silk proteins can self-
assemble into nanofibrils, which can be decorated with inorganic particles such
as metals or quantum dots [67, 124, 130-136]. Such decorated silk fibrils could
be used as nanowires [137, 138] or surface coatings [139, 140]. In addition, in
an approach similar to soft lithography, pouring the silk solution on to a pat-
terned substrate enables conformal replication of substrate features down to a