In the workgroup Preclinical Nanobiotechnology of the Fraunhofer Institute for Biomedical Engineering (IBMT) nanoparticulate formulations

• for specific drug targeting (e. g., tumor targeting) and
• for the crossing of biological barriers (e. g., blood-brain barrier) are tested in different cell cultures.

Special significance is given to specific particle systems circulating in the bloodstream for a long time and carrying a cell specific ligand. The ligand is directed against receptors which are especially expressed respectively over-expressed on the targeted tissue. Consequently, the nanoparticles are transporting the drug directly to the targeted cell without causing serious and unwanted side effects. The research and preclinical testing of nanoparticulate formulations for targeted tumor therapy is the main focus of our work. An additional important domain of medically efficient nanoparticulate formulations lies in the area of the blood-brain barrier research. Nanoparticles are able to mediate the transport of drugs via the blood-brain barrier. In the line of several projects different nanoparticulate formulations are researched. Corresponding cell culture systems are available at the IBMT. Special attention is given to drug-loaded (e. g., cytostatic drug) formulations for specific drug transport (»drug targeting«) with additional ligand modified surface. For the research of such particle systems first of all the kinetics of the cellular uptake and accumulation of the particle systems in cell cultures is of interest as well as their subcellular distribution. Methods like flow cytometry (FACS) and confocal laser scanning microscopy (CLSM) combined with corresponding competition and inhibition experiments are used. Afterwards, the particle degradation, drug release and biological efficiency of the nanoparticular transported drugs are verified with methods like fluorescence lifetime imaging microscopy (FLIM), different cytotoxicity tests (e. g., WST-1, LDH, BrdU) and individually developed assays. In this way new nanoparticulate formulations shall be found which mediate a target-oriented chemo therapy through selective cellular accumulation of the particle system bound drugs, respectively make a transport of drugs via the blood-brain barrier possible. In our studies we could demonstrate that such a specific targeting of functionalized nanoparticulate formulations is possible.

Different cell culture systems for the testing of related formulations are available for further projects.