Conventional drug administration often requires the application of high drug dosages to attain the biologically effective dose at the target tissue and causes massive side effects in non-target tissues. In contrast, drug delivery vehicles can direct biologically active substances to specific tissues and act as drug depot. Besides drug release kinetics from the carrier, also the biocompatibility of the drug carrier is of high importance, especially, if repeated administration is desired.
Spider silk is a suitable material for the development of high performance drug carrier. It is biocompatible, biodegradable, nontoxic and no immunogenic. Sub-micron particles made of the negatively charged eADF4(C16) are suitable carriers for neutral and positively charged model drugs. However, the polycationic version eADF4(κ16) is taken up much more efficiently into HeLa cells. These particles are suitable carriers of neutral or negatively charged molecules. Doxorubicin could be delivered into and released within cells. High-molecular-weight substances like nucleic acids were incorporated successfully into eADF4(κ16) particles and released in a controlled manner which makes these particles promising candidates for therapeutic gene delivery approaches. Further experiments showed that also the uptake rate of the negatively charged eADF4(C16) could be fine-tuned and significantly enhanced upon implementation of short peptides, such as RGD or the cell penetrating peptide Tat, allowing the efficient delivery of positively charged molecules. In summary, recombinant spider silk particles represent a versatile drug delivery system for various applications.