The research performed within the NanoMed consortium can be divided into three work packages. First, nanoparticles are produced which meet the criteria for application in nanomedicine. Secondly, these particles are investigated with regard to their interaction with living cells. Third, the scalability and in vivo behavior of the most promising nanocarriers is evaluated. The target diseases are cancer and age-related ocular pathologies, which are treated via administration of the particles in blood, in the peritoneum or via the lungs in case of cancer, and in the vitreous in case of ophthalmic diseases. On all different levels much progress has been made
A range of different particles has been created. Micelles, vesicles and nanogels have been prepared, for the transport of hydrophobic drugs and siRNA, respectively. Scalable nanocarrier preparation methods have been developed, which can be performed in an aqueous medium. Besides spherical particles, also tube-like morphologies have been created. As building blocks degradable synthetic polymers and polypeptides have been successfully employed. Furthermore, the surface properties of the particles have been fine-tuned for their biological application. These properties include pegylation and regulation of surface charge to prevent undesired interactions with the immune system; functionalization with targeting moieties for effective and selective cell uptake; and conjugation of therapeutic moieties to endow the particles with active cargo. As a result of these activities a library of well-defined particles has been created. Loading and release studies of model drugs has successfully been performed.
NanoMed ESRs have developed strategies to prolong circulation lifetime, stable self-assembled drug delivering micelles, the synthesis and characterization of photoactivating liposomes, RNA-delivering nanomaterial studies in serum, and the delivery of liposomes via intravitreal injection in the intact porcine eye. We are applying state of the art characterization techniques to understand and predict the material properties (particle stability, pH responsiveness, drug retention and release, and agglomeration) in in vivo-like environments. We have also investigated how nanocarriers interact with cells and how they have been taken up. Novel characterization tools, such as label-free Raman spectroscopy and high resolution Focussed Ion beam – Scanning Electron Microscopy (FIB-SEM) have been implemented to better understand the fate of particles upon entering living cells.
To evaluate the behavior of particles in an in vivo situation mathematical models and experimental procedures have been developed for nanocarrier distribution in the eye. Distribution of nanocarriers in the ex vivo bovine vitreous has also been monitored using histological approaches. Not only particle motion but also drug release has been evaluated and modeled with state of the art distribution models. A recently developed method for intraperitoneal nanomedicine administration has been applied to nanogels developed in the consortium. A much better distribution and colocalization with tumor cells was observed. Finally, one of the most promising polymer micelle particles was evaluated for its scalability in production. Both the synthesis of the block copolymers as the micelle formation process were optimized and it was demonstrated that this carrier system is a highly interesting candidate for the transport of hydrophobic drugs in cancer treatment.
