Analyzing Nanoparticle Shape to Infiltrate the Blood Brain Barrier

Current treatments for diseases of the brain are severely limited due to the seemingly impenetrable blood brain barrier (BBB). Recently, the use of nanoparticles has been shown to be a promising alternative for a variety of diseases, including cancer. These drug delivery vehicles hold great promise in transporting therapeutics across the BBB to treat neurodegenerative diseases, such as Alzheimer’s disease. Therefore, we examined how manipulating the physical properties of nanoparticles, such as shape and size, affect cellular internalization into brain endothelial cells, a major component of the blood brain barrier. To create nanoparticles of complex shapes, fluorescently-labeled 200 nm spherical polystyrene nanoparticles were first cast into polyvinyl alcohol and glycerol film and then stretched to form rod-like particles or flat discoidal particles. Thereafter, these particles were used to investigate the non-specific cellular uptake into mouse brain endothelial cells. Herein, the overall particle geometry was shown to significantly affect the rate of internalization into the brain endothelial cells. We hope to use these same principles to investigate if similar trends hold true for particles with targeting ligands for the BBB attached. We suspect finding the optimal particle shape to enter the BBB is the first step in predicting which particle geometry would deliver the highest therapeutic dose possible to the brain to treat neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.