Exploiting BBB disruption for the delivery of nanocarriers to the diseased CNS

The blood-brain barrier (BBB) segregates the central nervous system from the systemic circulation. As such, the BBB not only prevents toxins and pathogens from entering the brain, but also limits the brain uptake of therapeutic molecules. However, under certain pathological conditions, the BBB is disrupted, allowing direct interaction between blood components and the diseased site. Moreover, techniques such as focused ultrasound can further disrupt the BBB in diseased regions. This review focuses on strategies that leverage such BBB disruption for delivering nanocarriers to the central nervous system (CNS). BBB disruption, as it relates to nanocarrier delivery, will be discussed in the context of acute pathologies such as stroke and traumatic brain injury, as well as chronic pathologies such as brain tumors, Alzheimer's disease, and Parkinson's disease. Key aspects of nanocarrier design as they relate to penetration and retention in the CNS are also highlighted.