Challenges of Brain Targeting and Mechanism of Drug Transfer Across Brain Barriers

Both the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a crucial role in controlling the central nervous system (CNS) microenvironment. This is essential for maintaining the brain in optimal functioning conditions. The BBB is composed of endothelial cells lining the brain microvessels, while the BCSFB is formed by the choroid plexus epithelial cells. These barriers regulate the passage of both cells and molecules to and from the CNS via multiple mechanisms. They present specific transport processes, enzymes, and receptors while also displaying low passive permeability. This may be essential for brain function, but it also presents a challenge when targeting CNS diseases. The presence of the brain barriers is responsible for the high drug doses prescribed to increase the bioavailability in the site of action and consequently the rise in side effects. Thus, brain-targeting drug delivery systems will provide new methodologies for an efficient drug delivery across the brain barriers.