Crossing the Blood-Brain Barrier at the Nanoscale: Understanding the Influence of Physical Characteristics

As a variety of nanomaterials advance the treatment of various diseases including cancer, their utility to treat brain disorders remains an open question, owing to the exceptional barrier properties of the blood-brain barrier (BBB). Specifically, despite extensive studies on its biology, our understanding of the factors that influence nanoparticle translocation across the BBB is limited. To begin these investigations, we discuss our progress toward understanding the role of nanoparticles’ physical properties (e.g. size, shape, and flexibility) in their permeation across the BBB using in vitro models. Our microfluidic BBB platform recapitulates in vivo flow and architecture conditions while retaining sufficient simplicity to ensure a well-controlled environment. We demonstrate our ability to create and characterize these models, focusing on the device and protocol design. We also discuss the image analysis methods used to quantitatively measure particle transport in real time. The results provide important criteria to guide the rationale design of nanoparticles to facilitate their transport across the BBB.