Philipp Grad: Effects of gangliosides and PEG-lipids on the structure, properties and interactions of lipid self-assemblies

Abstract

When developing or utilizing lipid-based nanocarriers detailed structural characterization of the lipid self-assemblies, as well as in depth knowledge and control of their interaction with solids materials, is necessary to understand the behaviour. Disregarding one of the parameters can lead to misinterpretation of the results due to non-uniform samples or experimental artifacts caused by undesirable interactions with solid surfaces. 

Work included in this thesis show that gangliosides promote structural transitions of PEGylated liposomes to bilayer disks. The results suggest that the proposed ability of gangliosides to attenuate the anti-PEG immune response could be coupled to their ability to promote disk-formation.

The results of this thesis further emphasize the importance of processes taking place at the solution-solid interface between self-assembled lipid particles and solid surfaces. Silica surfaces were here of particular interest, and the results showed that PEGylated lipid nanocarriers, such as liposomes and lipodisks, spontaneously attach to the material. It was further shown that an elevation of the temperature can lead to irreversible structural changes, such as the formation of supported lipid bilayers. Interestingly, the investigations revealed that defect free supported lipid bilayers (SLB) can be formed from liposomes in the gel phase. 

The processes at the solution-solid interface are of relevance if the solute permeability of lipid membranes are investigated with the help of liposomes in combination with spectroscopic methods. Experimental artifacts resulting from processes at the solution-cuvette interface affect the measurements and impair the reliability of the results. In order to solve this issue we explored two methods to passivated the cuvette interface, and thus prevent, or minimize, the attractive interactions between the lipid particles and the cuvette walls. In the first case a PEG-polymer and in the second a SLB was used. Both methods have their individual advantages and our findings highlight the importance of a conscious selection of the experimental procedure.