Figure 1.

BBB structure and the development of therapeutics targeting the BBB. A) Historical timeline of key advances in understanding the BBB. B) The BBB is a key target for brain‐targeted therapeutics. 1) Disrupted BBB has been linked to the initiation and progression of neurological and cerebral vascular diseases. Restoration of BBB integrity may serve as a promising target for the treatment of these diseases. These strategies include the rescue of specialized tight junction in the brain endothelial cells, inhibition of transcytosis, and restoring efflux transporters. 2) The BBB remains a formidable obstacle to deliver drugs into the brain. Three major areas have been extensively explored to enhance brain‐targeted delivery: transiently opening of the BBB junction; inhibition of efflux transport and employment of transcytosis as a vehicle to facilitate transport. 3) Inflammation is a hallmark of brain diseases. Targeting inflammation restores the BBB, and BBB penetration is a prerequisite for therapeutics to fulfill potential in treating inflammation in the brain parenchyma. A combination of strategies in the restoration of the BBB and penetration of BBB are required to address the difficulties in the treatment of inflammation in the brain.