The barrier and interface mechanisms of the brain barrier, and brain drug delivery

Three different barriers are formed between the cerebrovascular and the brain parenchyma: the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB), and the cerebrospinal fluid-brain barrier (CBB). The BBB is the main regulator of blood and central nervous system (CNS) material exchange. The semipermeable nature of the BBB limits the passage of larger molecules and hydrophilic small molecules, Food and Drug Administration (FDA)-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Although the complexity of the BBB affects CNS drug delivery, understanding the composition and function of the BBB can provide a platform for the development of new methods for CNS drug delivery. This review summarizes the classification of the brain barrier, the composition and role of the basic structures of the BBB, and the transport, barrier, and destruction mechanisms of the BBB; discusses the advantages and disadvantages of different drug delivery methods and prospects for future drug delivery strategies.