Preparation and investigation of polyether and ester based functional block copolymers for biomedical applications

This work describes the synthesis and investigation of two different polymer systems, which are potentially suitable for the transport of nucleic acids, and can thus find use in (targeted) drug transport. On the one hand, a water-soluble and polyether-based AB diblock copolymer system that can form polyplexes with negatively charged pDNA was considered. On the other hand, a modification of this AB system to an ABC triblock terpolymer system was investigated, which can self-assemble into micelles by using a hydrophobic C-block. This allows said ABC system to potentially encapsulate nucleic acids such as siRNA. The AB system was synthesized by anionic ring-opening polymerization of allyl glycidyl ether (AGE) through block extension from polyethylene oxide (PEO) followed by modification with positively charged amine containing thiols. A targeting dye group was attached at the B-block by amide formation or at the α-position by incorporation of an α-ω-hetero-functionalized PEO. Polyplexes of these AB diblock copolymers with pDNA were investigated in in vitro experiments. The AB system formed herein a macroinitiator for the synthesis of a ABC system by block extension through tin(II) 2-ethylhexanoate [Sn(Oct)2] catalyzed ring opening polymerization of various lactones. Subsequently, primary and tertiary amines as well as an imidazole moiety were introduced by thiol-ene reaction. Aqueous solutions of self-assembled structures of these triblock terpolymers were equipped with the dye Nile Red and investigated upon their degradation behavior. Lastly, new dinuclear zinc-based bis(β-diketiminate) compounds that are biocompatible and nontoxic were studied as catalysts for the homopolymerization of caprolactone and its derivatives. The complexes were evaluated with respect to their reactivity as well as selectivity of the different bridges. Herein, the zinc containing compounds showed, compared to Sn(Oct)2 high reaction rates at relatively low temperatures.