The highly secure blood-brain barrier (BBB) restricts drug access to the brain, limiting the molecular toolkit for treating central nervous system (CNS) diseases to small, lipophilic drugs. Development of a safe and effective BBB modulator would revolutionise the treatment of CNS diseases and future drug development in the area. Naturally, the field has garnered a great deal of attention, leading to a vast and diverse range of BBB modulators. In this review, we summarise and compare the various classes of BBB modulators developed over the last five decades-their recent advancements, advantages and disadvantages, while providing some insight into their future as BBB modulators.
Keywords: BBB modulation; BBB permeability; CNS drug delivery; alzheimers; blood-brain barrier (BBB); focused ultrasound; glioblastoma; hyperosmolar agents; intra-arterial drug delivery; tight junction (TJ).