Blood–brain barrier and nanovesicles for brain-targeting drug delivery

The blood–brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs) in close cooperation with other cells (astrocytes, pericytes, and neurons) and the extracellular matrix, selectively controls the brain transportation of the blood-circulating substances such as nutrients and drug molecules. Such discriminative blockage can make the delivery of drugs into the central nervous system (CNS) a big challenge. The complex settings of different cells form a cooperative neurovascular unit (NVU), in which BCECs play a key role in terms of brain homeostasis and maintenance. Of different approaches exploited to deliver drugs into the CNS, nanoscale smart drug delivery systems are the most successful systems. Of note, multimodal nanovesicles (NVs) can be designed and developed as lipid-/polymer-based nanomedicines that can be further decorated with targeting and imaging. For the ultimate brain targeting and therapy, NVs should be designed as dual-targeting nanosystems to cross the BBB through receptor-mediated transcytosis and to actively target the diseased cells. The use of microfluidic technologies has revolutionized the homogenous production of different types of lipid- and polymer-based NVs as well as the isolation of cell-derived vesicles. This chapter describes various types of NVs and offers deep insights into the multifunctional NVs for active targeting and imaging and treatment of the unhealthy cells in the brain.