Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for... Show moreUtilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric building blocks, desired application and cargo, the final nanoparticles always combine a polysarcosine (pSar) shell with a polypeptide core, providing the ability of siRNA complexation by a polycationic segment. In addition, a third block enabled either covalent cross-linking, hydrophobic / π- π-stacking mediated stabilization or co-encapsulation of small hydrophobic drugs. Broadening the structural variety of such polypept(o)ides, a novel synthetic procedure was introduced to access AA'B- and ABC-type miktoarm star polymers.Investigations have been dedicated to the design of novel polymeric structures based on polypept(o)ides, to improve the delivery of siRNA by Polyion Complex Micelles (PICMs), provide access to different polymeric architectures, and to establish novel synthetic methods for the synthesis of these materials. Covering aspects from the synthesis of novel polymeric species up to advanced drug delivery strategies for siRNA in vivo, developments throughout this thesis extent the accessibility of the polypept(o)ide platform for nucleic acid delivery, highlight their potential in nanomedicine and further elaborate delivery strategies for next-generation nanomedical applications. Show less
Heestermans, M.; Jong, A. de; Tilburg, S. van; Reitsma, P.H.; Versteeg, H.H.; Spronk, H.M.; Vlijmen, B.J.M. van 2019
Formation of the epidermal barrier is a complex process involving the tight regulation of the expression of structural proteins, enzymes and cytokines, implementing different signaling pathways... Show moreFormation of the epidermal barrier is a complex process involving the tight regulation of the expression of structural proteins, enzymes and cytokines, implementing different signaling pathways depending on the differentiation stage of KC. Alterations of skin barrier formation occur as consequence of many skin diseases but can also be the primary event leading to skin diseases. Organotypic skin models have greatly contributed to delineate molecular mechanisms underlying the epidermal differentiation process. In this thesis we have adapted a human organotypic skin model to knock-down individual genes and study their impact on the differentiation of epidermal KC in vitro. Using this model we have provided new insights in the formation of the skin barrier of human skin. Show less
