Antibody delivery through the blood-brain barrier

The diagnosis and therapy of diseases of the central nervous system could benefit from the application of highly specific monoclonal antibodies as drugs. There is, however, the pharmacokinetic problem of delivering these high molecular weight proteins through the blood-brain barrier (BBB). Because the size of even small antibody fragments (Fv, Fab) severely limits attempts to increase the delivery by passive diffusion through the intact BBB, methods that are under evaluation try either to circumvent the barrier by direct administration into cerebrospinal fluid or brain tissue, or to disrupt the barrier temporarily by hyperosmotic solutions. Both approaches require invasive techniques. Alternatively, cationization of antibodies may enable them to undergo physiological processes of active transport, such as absorptive mediated transcytosis. Examples are presented, where the respective target antigen belongs to a different category of disease: a neurodegenerative process, viral disease, and tumors. Cationized antibodies may target extracellular antigens, or access intracellular space and exert intracellular immunization.