I. Introduction
The EXCHANGE of molecules across the cerebral microvasculature is regulated by a unique interface known as the blood–brain barrier (BBB). Its major functions are to prevent toxins from entering the parenchyma and to maintain molecular environments necessary for proper neuronal firing [1], [2]. Through a combination of passive, transport, and metabolic barriers, nearly all systemically administered compounds larger than 400 Da are excluded from the brain's extracellular space, rendering thus many neurologically potent compounds ineffective [3]. As a result, potential therapeutic agents, such as inhibitors to enzymes (1 kDa) and antibodies (30–300 kDa), will not reach their intended targets if administered systemically. The treatment of central nervous system (CNS) disorders will remain severely impaired until a method to deliver such large agents in the brain at a sufficient dose is shown to be effective [3].