Abstract
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 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 for drug delivery. Here, a new method was established for particle production to reduce particle size and size distribution. Importantly, cellular uptake of these particles was shown to be poor in HeLa cells. Therefore, variants of eADF4(C16) with inversed net charge or incorporated cell penetrating peptides and receptor interacting motifs were tested, showing much better cellular uptake. Interestingly, uptake of all silk variant particles was mainly achieved by clathrin-mediated endocytosis.
Highlights
In principle drug delivery systems allow the achievement of constant drug levels at targeted locations within the body
Materials made of recombinantly produced spider silk proteins or silkworm fibroin have been shown to be well tolerated by cells.[11,12,13,14,15,16]
Particles made of eADF4(C16) have been previously used as drug delivery vehicles. eADF4(C16) is based on the repetitive core domain of the spidroin ADF4 of the European garden spider Araneus diadematus and can be processed into different morphologies including films,[17,18] hydrogels,[19] non-woven mats,[20] capsules,[21,22] and particles.[23,24]
Summary
In principle drug delivery systems allow the achievement of constant drug levels at targeted locations within the body. Materials made of recombinantly produced spider silk proteins or silkworm fibroin have been shown to be well tolerated by cells.[11,12,13,14,15,16] In this respect, particles made of eADF4(C16) have been previously used as drug delivery vehicles. HeLa cells were cultured on treated 6-well cell culture plates (Nunc, Langenselbold, Germany) with a density of 30 000 cells cm−2 in the presence of spider silk or control fluorescent particles for 6, 24, 48 and 72 h.
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