Morphological transitions in langmuir films of a diblock copolymer from polyethylene glycol and poly-L-lactide
Emna Khechine. Inaugural-Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie, 2021
Lipopolymers which are composed of lipids covalently linked to polyethylene glycol (PEG) head groups, have been used to improve the stability of bilayer membranes which is a necessary property for the preparation of drug carriers. Furthermore, the presence of PEG increases the circulation time of the pharmaceuticals. PEGylated vesicles can also be prepared from amphiphilic diblock copolymers and a direct incorporation of the agent into such vesicles becomes possible. It has been shown that an increased therapeutic effect of the drug can be achieved through conjugation with PEG over a relatively broad range of chain length and admixed portions of PEG. However, the exact mechanisms responsible for this PEG induced effects are not yet known. On the other hand, a certain risk of an immune defence reaction (immunogenicity) against PEGylated drugs has also become apparent, which makes it necessary to identify the optimum amount of PEG moieties on surfaces. PEG molecules may reside on a surface and take different conformations depending on grafting density, length of the PEG chains and their interactions with surrounding water molecules. Due to these multiple parameters, such a system is complex and difficult to control. One possible approach is to reduce its complexity and to design experiments that allow for a precise adjustment of certain parameters. A simplified and easily controllable system is a Langmuir film which can be prepared in different phases through a precisely adjustable surface density. Accordingly, experiments on Langmuir films can provide useful information on the topic of the correlation of surface density and interactions between molecular units and the resulting physical properties.
In the here presented work, we investigated morphological transitions upon compression of Langmuir films of a diblock copolymer composed of two short blocks of methyl-terminated PEG (mPEG) and poly-L-lactide acid (PLLA). These two blocks are balanced in terms of molecular weight and therefore also in terms of hydrophilicity and lipophilicity (HLB value). Due to this well-balanced HLB value, one may expect the formation of regularly arranged structures as for example micelles. At rather high surface densities, the morphologies observed in the Langmuir films showed a transition from curved fibers arranged in regularly spaced circles to straightened fibers that were preferentially aligned parallel to each other. This transition passed through an intermediate state of randomly oriented short fiber-like structures. We also investigated the influence of changes of compression rate and temperature on the behavior of the diblock copolymer in Langmuir films. Surprisingly, only the transition from circular to parallel arranged fibers showed a dependence on the rate of compression while the other regions of the isotherm were not affected. Upon increasing the temperature, this transition was shifted towards a higher surface pressure and a smaller area per molecule. The temperature dependence of the interactions between PEG and water was considered to be responsible for this observation. By studying the miscibility of the homopolymers mPEG and PLLA in Langmuir films, we have clearly identified repulsive interactions between these polymers, allowing for the conclusion that, in Langmuir films of the block copolymer, PLLA and PEG phase-separated and arranged above and below the air/water interface, respectively. Accordingly, the mPEG chains formed a layer in the sub-phase region, which, due to the covalent links to the PLLA chains, was forced to stay close to this interface. With increasing surface density, the PLLA chains ordered at the interface with an interspacing governed by the hydrodynamic volume taken by the PEG blocks. The mPEG chains underwent conformational transitions in water and stretched into the sub-phase at the highest compression, which we interpreted as a transition from a PEG quasi-brush regime to a PEG brush induced by compression. Compression-expansion experiments showed that this transition was reversible as demonstrated by the re-appearance of well assembled circular arrangements of fibers upon expansion of a film that was previously compressed into the brush state. Finally, we have studied the influence of the molecular weight of PLLA on structure formation of the diblock copolymer, concluding that curved fibers were present for all mPEG2000-PLLA diblock copolymers used in this study. The curvature of the fibers was attributed to the increased surface stress which was reinforced by a mismatch in size of the two polymer blocks. The regular array of well arranged circular fibers, however, was only observed for the block copolymer with balanced molecular weights.