Main Results

Overall, the project succeeded to fulfil all expectations and produced many results of both scientific and industrial significance with relevant socio-economic impact.

1. An innovative production technology was established to generate liposomes or nanocapsules as a drug delivery system with very high encapsulation efficiencies using centrifugation both as a batch process and a continuous process ready for industrial scale-up. Breakthrough was achieved by elucidating the colloidal properties of membrane lipids at interfaces to prepare the formation of novel asymmetric bilayers.
2. The versatility of the encapsulation technologies could be shown exemplarily for different classes of proteins to model hydrophilic sensitive biomolecules which are vulnerable to degradation by thermal, pH or organic solvent conditions used in existing encapsulation technologies.
3. Tailor-made nanocapsule shells of lipid bilayers were proved to be achievable to allow different functionalities for the inside and outside leaflets of the shells. A proof was shown using a batch process which can now be transferred to a continuous process.
4. Complete encapsulation was approached with high encapsulation efficiencies up to 95%. The system can now be adapted to industrial conditions and scale-up, for which a suitable framework could be established.
5. A novel coating system for liposomes or nanocapsules was developed based on heparin, a human polysaccharide, i.e. a glycosaminoglycan. Heparin showed clear advantages compared to the current standard coating by polyethylene glycol (PEG) with respect to much lower activation of the complement system in a human whole blood model. The results achieved will enable in the future to produce liposome or nanocapsule coatings which are small enough in their coating thickness. A reduced size is necessary to enable long circulation without provoking any innate or specific immune reactions by the complement, the coagulation and the phagocytic systems. Such a novel coating system is still a major unsatisfied demand since accelerated blood clearance upon repeated administration occurs with PEG as own in vivo tests show.
6. Testing of the novel drug delivery system was performed for stability in human blood in vitro. The investigation of the encapsulated showcase API, mistletoe lectin, elucidated the so-far unknown specific endocytosis mechanisms in murine and human cancer cells in vitro. The release of API from liposomes was studied and different mechanisms to increase release using thermosensitive liposomal membranes were established. Half maximal inhibitory concentration (IC50) were tested for different cell lines. A variety of immune reactions on liposomes were investigated.
7. Multidisciplinary research was efficiently enabled by the collaboration of 3 renowned universities and a medium sized, internationally-active pharmaceutical company.