Grant: Collaborative Health Research Projects (NSERC partnered)

Effective treatment of brain related disorders requires an adequate distribution of drugs into the brain. For many drugs, penetration into the brain is restricted by the brain capillaries that form what is referred to as the blood-brain barrier (BBB). The current research project will develop iron-oxide based nanoparticles as a delivery platform for enhancing the brain penetration of drugs. Our approach is to utilize the magnetic properties of the nanoparticles to "pull" them through the BBB by applying a magnetic field to the brain. Optimization of the outer surface properties of the magnetic nanoparticles will be performed to target the nanoparticles to the junctions between the brain capillary endothelial cells which in the presence of a magnetic field will enhance BBB penetration. Once optimization is achieved, studies will be preformed to determine the bio-compatibility and safety profile of these magnetic nanoparticles at both the cell culture and whole animal (mouse) level. This is important as the potential brain related toxicity of these particular nanoparticles is unknown. Finally, using a prototype magnetic nanoparticle, we will perform proof-of-principle studies demonstrating the increased delivery of chemotherapeutic agents to target sites in a mouse brain tumor model. Our overall objective is to determine the optimal surface properties and magnetic field strengths to achieve brain penetration, as well as to characterize the bio-compatibility and safety profile of these magnetic nanoparticles for brain related applications.