Governing Transport Principles for Nanotherapeutic Application in the Brain

Neurological diseases account for a significant portion of the global disease burden. While research efforts have identified potential drugs or drug targets for neurological diseases, most therapeutic platforms are still ineffective at reaching the target location selectively and with high yield. Restricted transport, including passage across the blood-brain barrier, through the brain parenchyma, and into specific cells, is a major cause of ineffective therapeutic delivery. However, nanotechnology is a promising, tailorable platform for overcoming these transport barriers and improving therapeutic delivery to the brain. We provide a transport-oriented analysis of nanotechnology's ability to navigate these transport barriers in the brain. We also provide an opinion on the need for technology development for increasing our capacity to characterize and quantify nanoparticle passage through each transport barrier. Finally, we highlight the importance of incorporating the effect of disease, metabolic state, and regional dependencies to better understand transport of nanotherapeutics in the brain.