Synthesis and Aqueous Self-assembly of Atactic and Isotactic Poly(butylene oxide)-block-poly(glycidol) Diblock Copolymers

Aqueous self-assembly of amphiphilic block copolymers (BCPs) is studied extensively for biomedical applications such as drug delivery, nano- or microreactors or artificial cell mimics. The commonly used poly(ethylene glycol) (PEG) as hydrophilic block and poly(dimethyl siloxane) (PDMS) as hydrophobic block suffer from several drawbacks regarding synthesis, reproducibility or biocompatibility. As potent alternatives, poly(glycidol) (PG) as hydrophilic block and poly(butylene oxide) (PBO) as hydrophobic block have gained increasing interest, benefiting from their easy synthesis, high biocompatibility and flexibility. In this thesis, a quick and well-controlled microwave-assisted synthesis of poly(butylene oxide)-block-poly(glycidol) (PBO-b-PG) amphiphilic BCPs is presented together with a straight-forward self-assembly protocol. Depending on the hydrophilic mass fraction of the BCPs, nanoscopic micelles, worms and polymersomes (Small Unilamellar Vesicles, SUVs) were formed as well as microscopic giant unilamellar vesicles (GUVs). The self-assemblies were analysed regarding their size and shape, using a combination of light scattering and electron and fluorescence microscopy techniques. A strong dependence of the formed morphology on the self-assembly method was discovered, proving that only solvent exchange led to the formation of homogenous phases.
Additionally, this work takes advantage of the possibility to introduce chirality into the PBO-b-PG backbones to create fully isotactic BCPs. The commonly used isotactic BCPs such as poly(L-lactic acid) or poly(propylene oxide) typically exhibit (semi-) crystalline behaviour, inducing high membrane stiffness and limiting their applicability in systems involving membrane proteins or sensitive cargo. Here, isotactic yet fully amorphous PBO-b-PG BCPs are introduced in order to overcome these limitations. Three PBO-b-PG BCPs, differing solely in their tacticities (R/S, R and S), were synthesised and characterised regarding their structural, optical and thermal properties. Their self-assembly into homogenous phases of SUVs was analysed, revealing stability differences between SUVs composed of the different BCPs. Additionally, GUVs were prepared by double emulsion microfluidics. Only the atactic BCP formed GUVs which were stable over several hours, whereas GUVs composed of isotactic BCPs ruptured within several minutes after formation. The ability of atactic PBO-b-PG to form microreactors was elucidated by reconstituting the membrane protein OmpF in the GUVs membrane and performing an enzyme reaction inside its lumen. A comparison with the established PDMS-b-PMOXA revealed that PBO-b-PG GUVs were more permeable to hydrophilic substrates. Hence, this study sets the basis to create functional nano- or microreactors composed of fully amorphous isotactic BCPs. It allows to assess how BCP tacticity affects the formation, morphology, stability and membrane thickness of SUVs and GUVs without affecting the membrane flexibility. This, in turn, will open a path to access interaction of the membrane forming isotactic BCPs with chiral cargo or chiral membrane proteins.