3 Blood-Brain Barrier

The brain is a unique organ highly protected by two major barriers, the BBB which displays the largest surface area and the blood–cerebrospinal fluid barrier (BCSFB). BBB is responsible for several functions, such as maintenance of neuronal microenvironment, tissue homeostasis, vasotonous regulation, fibrinolysis and coagulation, blood cell activation and migration during physiological and pathological processes. There are several gateways which offer entry to brain parenchyma, the most important are blood circulation and cerebrospinal fluid (CSF) circulation. In the human brain, there are about 100 billion capillaries in total, providing a combined length of brain capillary endothelium of approximately 650 km and a total surface area of approximately 20 m2 [12]. Despite the rapid development in understanding of the molecular structure of components of the BBB, knowledge of receptor expression at the BBB, advances in medical technology, and breakthroughs in nanotechnology-based approaches, many of the CNS associated diseases remain under-treated by effective therapies. Since the majority of drugs and large molecular weight particulate agents such as recombinant proteins, peptides, monoclonal antibodies, small-interfering RNA (siRNA) and gene therapeutics do not readily permeate into the brain parenchyma, one of the most significant challenges facing CNS drug development, is the availability of effective brain drug targeting technology.