The layer-by-layer (LbL) technique is a versatile methodology, which involves the sequential assembly of building blocks of diverse nature, such as natural and synthetic polymers, nanoparticles, biomacromolecules, etc. to fabricate sophisticated nanostructures with potential use in drug delivery and tissue engineering applications. In this Thesis, synthetic polypeptides are used as building blocks to develop polypeptide-based multilayered systems at the micro- and nano-meter scale and explore three different strategies relevant for both drug delivery and tissue engineering applications. In Chapter 3, three different methodologies are developed to incorporate poorly water-soluble drugs into polypeptide-based multilayer microcapsules and increase drug solubility and bioavailability. The second strategy, described in Chapter 4, relies on the decoration of the external layer of polypeptide-based multilayer nanoparticles for skin wound healing applications. Specifically, the effect of the outer layer in both cellular uptake and wound repair has been explored, observing an enhanced tissue repair when hyaluronic acid is in the external layer. Finally, in Chapter 5, multilayer microreactors are developed including a polymer-hybrid enzyme into the core or the self-assembled nanostructure to explore their antioxidant and therapeutic properties. Overall, the findings reported in this Thesis represent an initial assessment in the perspective to gather different strategies in a unique highly engineered multilayer system with potential application for both drug delivery and tissue repair.
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