Amphiphilic block copolymers in aqueous and nonaqueous emulsion systems for biomedical Applications

Abstract

The overall scope of this thesis was the investigation of nanoparticle behaviour in biological environment in respect of the particle surface composition. Divided into polar-ionic and polar-nonionic surfaces, different materials were synthesized in order to investigate their stability and aggregation behaviour in aqueous solution as well as the interactions with biomolecules like serum proteins or cells. The gained knowledge was used to evaluate different technologies to develop a potent drug carrier system for biomedical applications. The scope of this thesis, to study the influence of surface chemistry on interactions with biomolecules as well as developing a feasible drug delivery device based on the knowledge about these interactions, was well addressed. Progress was made in the investigation of charged surfaces and protein interactions. The synthesis of amphiphilic PMA-based terpolymers with differing charged side chains for the coating of gold nanoparticles was performed successfully within this thesis. It was found that the zwitterionic MPC-based polymers indeed had anti-fouling properties against protein corona formation. Cell viability tests showed good results for all four polymer-coated quantum dots. Stability studies proved that the zwitterionic materials have valuable anti-fouling properties towards main components of human blood serum and good stability in biological media. In addition, many interesting and positive results were obtained on the functionalization of the serine side chain and its polymerization and aggregation behaviour in aqueous and nonaqueous media. Especially the O-pyrenyl-serine derivative turned out to be a promising building block for the synthesis of amphiphilic, photo-responsive block copolymers. These performed very well as emulsifiers in the first attempts of nonaqueous emulsion polymerization and resulted in homogeneously dispersed nanoparticles of uniform size, allowing the design of dual-responsive core-shell nanoparticles for drug delivery applications. Good results were obtained by using PEG b PSer(Bn) block copolymers for the synthesis of vesicular assemblies. They showed excellent stability in aqueous solution and biocompatibility as well as promising initial results in cell uptake experiments. Drug loading with doxorubicin was performed successfully and the DOX-loaded carriers showed good cell viability. This comparably simple drug delivery system was stable in biological environment, if no trigger mechanism was incorporated into the carrier. It bears the chance to build a potent carrier to safely deliver a drug into the tumor tissue without drug leakage, followed by a controlled release of the drug at the target tissue. Overall, this thesis provided a solid basis of results on the development of serine-based drug delivery systems, deserving further investigation to achieve the goal of developing an innovative drug carrier system and overcome the beforementioned drawbacks that were faced during the research.