The Blood–brain barrier (BBB) is a highly selective semipermeable frontier of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.
BBB has been a great barrier to brain drug delivery. This is a healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds across the blood to the brain and only small molecules can cross the BBB.
A blood-brain barrier maintains homeostasis by obstructing toxic molecules from the circulation, but drugs are blocked at the same time. When the dose is increased to enhance the drug concentration in the central nervous system, then there will be side-effects on peripheral organs. In recent years, genetic therapeutic agents and small molecules have been used in various strategies to penetrate the BBB while minimizing the damage to systemic organs.