PROJECT: JTC2009: NanoBrain

The number of people suffering from Alzheimer?s disease (AD) is estimated to be around 11.2 million Europeans by the year 2050. To date, there are no effective treatments to relieve the burden of this devastating neurodegenerative disease that causes cognitive impairment and memory loss, either for the concerned patients or for society. Present pharmacological treatment for AD is symptomatic in nature and does not modify the course of the disease. The progressive nature of AD indicates that future therapies should aim at prevention as such or halting further progression of the disease at very early stages, rather than treatment in advanced stages. Any drug for such prevention needs to fulfill two critical requirements. First, the drug should target underlying molecular and biological mechanisms responsible for initiation or initial steps of the disease process. Second, the drug should have minimal sideeffects and the potential to enter the brain. Since potential drugs against AD have been successfully tested in vitro but failed in patients due to minimal blood brain barrier (BBB) penetrance, we will develop in this project a transport model that might help to understand transport of AD drugs into the brain. Our research consortium will focus on the establishment of in vitro BBB models to determine the kinetics of receptor mediated nanoparticle transport. These kinetic data will be instrumental for the use of the in vitro BBB model to transport AD drugs e.g. non-steroidal anti-inflammatory drugs (NSAIDs) loaded on nanoparticles. After establishing the drug transport we will measure the drug release and the biological activity of the released AD drug in tissue culture models. To identify the transport mechanisms we will investigate the nanoparticle transport on a single cell level and monitor nanoparticle transport using micro-optic techniques. Additionally, we will try to develop an in vivo approach to follow nanoparticle transport in living animals using MRI technology. The overall objective of this project is to develop novel drug delivery systems based on nanoparticles for the specific transport of AD drugs over the BBB.