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
This thesis aimed to investigate core cross-linked polymeric micelles (CCPMs) and expand their potential for the delivery of hydrophobic drugs and co-factors. Applying polypept(o)ides as the... Show moreThis thesis aimed to investigate core cross-linked polymeric micelles (CCPMs) and expand their potential for the delivery of hydrophobic drugs and co-factors. Applying polypept(o)ides as the polymeric platform technology, the fundamental implications of secondary structure formation on ring-opening N-carboxyanhydride (NCA) polymerization and self-assembly were examined and optimized. CCPMs with functional core architectures serving external or disease-related stimuli were developed. To establish robust CCPM production, overcome drug resistance mechanisms, and explore therapeutic agents for immunomodulation, polymer science was combined with organic and inorganic chemistry. Show less
