Programmed Drug Delivery

The objective is to develop nanostructured smart drug delivery devices capable of bypassing extra- and intracellular biological barriers, to understand the targeting and delivery mechanism on a single particle level, and to apply the new materials in pharmacological models. ‘Smart’ nanosystems will be pre-programmed to alter their structure and properties during the drug delivery process, to make them most effective and specific for the different delivery steps. Innovative matrices for nanosystem assembly will include hollow elastic colloidosome or recombinant spider silk protein capsules with highly controllable permeability, functionalized nanoporous silica devices, polyelectrolyte complexes of bioactive polymers, and combinations thereof. Delivered drugs will be chemical substances, peptides, proteins or therapeutic nucleic acids (DNA, siRNA). For controlled loading and release of drugs matrices will be functionalized, internally with drug binding hosts or with bioreversible bonds for controlled matrix degradation, and at the particle surface with ligands attached for targeting purposes and reactive caps for drug release at the locus of activity. Target specificity can be enhanced by combining biochemical targeting (receptor binding) with physical targeting (magnetic, ultrasound or photo-chemical targeting). Biophysical characterization of smart nanosystems will be accompanied by cell interaction studies such as single particle live cell imaging. Therapeutic efficacy will be studied in established pharmacological in vivo models for tumor targeting, cardiovascular or neurodegenerative diseases. The transfer of basic research efforts tailoring new nanostructured materials to in vivo applications is in the centre of the proposed initiative.