Vesicles form naturally in cells and can do many things, including transporting pharmaceutically active substances to tumours. However, natural vesicles only have a short lifespan, which can lead to the premature release of the drug enclosed within them. Alexander Wittemann, a chemist at Konstanz University, has successfully developed artificial biocompatible polymer vesicles with a much longer lifespan. They open up new possibilities for the sustained and delayed release of drugs into the body as well as for the application of cosmetic products on the skin. Wittemann is also investigating the movement of complex particles on self-composed clusters of polymer particles. Wittemann’s findings are of importance for protein immobilization and diffusion movements of biomolecules, amongst other things.
Proteins are transported around the body by way of vesicles, small bubbles enclosed by a membrane. This natural transport system can also be used in medicine to transport drugs to their target (e.g. tumours). “The vesicle membrane encloses the drugs, thereby protecting the cargo against enzymatic degradation,” Prof. Alexander Wittemann, chemist at the University of Konstanz, explained. However, the short lifespan of liposomes (artificially-prepared vesicles composed of a lipid bilayer) can cause the premature release of drugs. Wittemann knows how to counteract this situation and has developed a method that enables him to produce artificial polymer vesicles that are more robust at the same time as having a much longer lifespan than liposomes.
Wittemann’s polymer vesicles can be biologically degraded: the membrane that surrounds the vesicles is degraded by way of hydrolysis, leading to the release of the enclosed drugs. “The lifespan of the aggregations can be controlled by varying the wall thickness of the vesicles, which makes them suitable tools for the controlled and delayed release of drugs,” Wittemann said. Vesicles can be used for many things, including as ingredients in cosmetics products where they regulate the uptake of water-soluble drugs or the uptake of fragrances into the skin. In the field of biomedicine, vesicles can be used for transporting drugs as well as for the transfer of genes. “We can also envisage the use of the small vesicles as microreactors, i.e. tiny test tubes to achieve small-volume reactions,” Wittemann added.
Artificial polymer vesicles form in a solution of drugs or biomolecules. Due to their unique structure, they are capable of encapsulating such hydrophilic moieties. “We have produced block copolymers with a central polycaprolactone block. The vesicles form in an aqueous solution after several hours of stirring,” Wittemann said. The use of polycaprolactone, a biologically degradable polyester, does away with solvents which would otherwise destroy proteins. Proteins are attached to the walls of the vesicles in order to prevent the agglomeration of the vesicles. “This effect is exploited for example in diagnostic applications in order to suppress the unspecific agglomeration of particles,” said the chemist.
Another of Wittemann’s projects focuses on finding out how the shape of particles or larger molecules (e.g. proteins) affects their movement. Wittemann produces particle clusters of complex but clearly defined shapes using spherical polymer particles. “Our observations are of fundamental importance for understanding deposition processes, the development of particle clusters and flow behaviour,” Wittemann explained. The polymer particles are produced from particles around 100 nanometres in size, which Wittemann then combines into different shapes. Amongst other things, his findings on the movement of microscopic vehicles used for the transport of drugs or on the immobilization of proteins are important for his research work. The model system also provides information on the spatial distribution of proteins, ribosomes and entire cells.
The defined geometry of the particle clusters enables movement predictions to be made using hydrodynamic models. Although the models were developed for proteins, the naturally flexible protein structures nevertheless lead to differences between experimentally observed and predicted movements. Although they are complex in shape they are also regular, so polymer particles are more suitable for such predictions. “We found that our experimental observations and theoretical predictions matched quite well,” said Wittemann.
Prof. Dr. Alexander Wittemann did his doctorate at the University of Karlsruhe on “protein immobilization through adsorption on polyelectrolyte brushes”. He is mainly interested in polymers, nanoparticles and proteins and he also focused on this issue during a research stay at McGill University in Montreal as well as at the University of Bayreuth where he dealt with the secondary structure of proteins in polymeric nanostructures. He has been professor of colloid chemistry at the University of Konstanz since 2011.