Engineering of Recombinant Spider Silk Proteins Allows Defined Drug Uptake and Release

摘要

Drug delivery systems allow tissue / cell specific targeting of drugs in order to reduce total drug amounts administered to an organism and potential side effects upon systemic drug delivery. Most drug delivery systems are polymer-based, but the number of possible materials is limited since many commercially available polymers induce allergic or inflammatory responses or lack either biodegradability or the necessary stability in vivo. Spider silk proteins represent a new class of (bio)polymers that can be used as drug depots or drug delivery systems. The recombinant poly-anionic spider silk protein eADF4(C16), which can be processed into different morphologies such as particles, films, or hydrogels, has been shown to fulfil most criteria necessary for its use as biomaterial. Further, eADF4(C16) particles have been shown to be well-suited as drug carriers for poly-cationic or neutral drugs, but cellular uptake of such particles is low. Novel variants of eADF4(C16) with inversed net charge or incorporated cell penetrating peptides and receptor interacting motifs show an increased cellular uptake. Further, poly-cationic variants allow incorporation of negatively charged drugs including high molecular weight substances, like nucleic acids.