Linear AB and ABC amphiphilic block copolymers : from synthesis to complex self-assembled structures

Every living organism depends on functional macromolecules assembled in aqueous solution via noncovalent interactions. Hydrophobic forces are particularly stable among other noncovalent interactions, which led to the development of amphiphilic synthetic (macro)molecules able to self-assemble into various structures for diverse applications ranging from nanotechnology to medicine. Amphiphilic block copolymers are especially advantageous due to the control over their properties achieved via tuning the chemical composition and superior stability of the self-assembled structures compared to the ones formed by low molecular weight surfactants and lipids. Particularly, structures formed by biocompatible and/or biodegradable amphiphilic block copolymers possess required properties for drug delivery applications.
Self-assembly of various AB (A – hydrophilic, B – hydrophobic) copolymers has been explicitly investigated with respect to the packing geometry of individual polymer molecules and conditions of self-assembly. Introduction of the third C block increases the level of complexity of self-assembly behavior of ABC copolymers. ABC copolymers provide possibility for developing programmable materials based on asymmetric structures with spatially separated domains possessing different chemical and physical properties. For example, multicompartment morphologies, i.e. assemblies bearing domains in the core, can be obtained in a solvent which selectively solubilizes A block, whereas B and C blocks undergo phase separation in the core. ABC copolymers with A and C soluble blocks are advantageous for creating structures with surface bearing domains in the corona, but the principles of self-assembly of such systems still lack deep understanding.
The ultimate goal of this thesis is to shed light on the complex morphological behavior of linear amphiphilic ABC copolymers with A and C water-soluble blocks targeting for biomedical applications. To approach this goal, synthesis of ABC copolymers bearing biocompatible blocks (poly(ethylene oxide) PEO, poly(2-methyl-2-oxazoline) PMOXA), biodegradable blocks (polycaprolactone PCL, poly(γ-methyl-ε-caprolactone) PMCL), and cationic block for complexation of nucleic acids (poly(N,N-dimethylaminoethyl methacrylate) PDMAEMA) is developed. Then, the complex self-assembly behavior of synthesized copolymers is investigated. Details of the synthesis and self-assembly behavior are summarized in three publications and one section of this thesis.
The first publication presents an optimization of the seemingly well-known synthesis of PEO-b-PCL. The optimization was a necessary step for the development of the toxic-free synthesis of PEO-b-PCL-b-PMOXA copolymers. The procedure for obtaining PEO-b-PCL with narrow dispersity (ÐM < 1.1), its ω-tosylation, and the effect of aging of the catalyst, SnOct2, on this polymerization is described. In addition, we have shown that lowering the dispersity of PEO-b-PCL results in more uniform self-assembled structures.
The second publication describes the synthesis of PEO-b-PCL-b-PMOXA with fixed PEO and different PCL and PMOXA lengths. The self-assembly of these polymers was tested in aqueous solution using film rehydration method. PEO-b-PCL-b-PMOXA self-assembled into various structures, including polymersomes. The polymersomes possessed asymmetric membrane: a longer PEO block formed the outer corona, a shorter PMOXA block formed the inner corona. The asymmetry of the membrane was proven by two independent methods.
The third publication aims to elucidate the general principles of aqueous self-assembly of bis-hydrophilic PEO-b-PCL-b-PMOXA copolymers. Self-assembly was investigated with respect to different PCL and PMOXA lengths using three different preparation methods: film rehydration, solvent evaporation, and co-solvent. The diversity of the formed structures is discussed in terms of the packing geometry and thermodynamic/kinetic control.
Finally, the fourth section describes synthesis and self-assembly of PEO-b-PRCL-b-PDMAEMA copolymers, where R is methyl (M) or phenyl (Ph). The self-assembly regarding the hydrophobicity of the middle block was investigated. Different hydrophobicity did not affect the morphology of the assemblies, but led to the increased size of the structures formed by more hydrophobic PEO-b-PPhCL-b-PDMAEMA compared to PEO-b-PMCL-b-PDMAEMA. These polymers are of particular interest for gene delivery applications due to the presence of cationic PDMAEMA block.