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Sudhir Majgainya, Shashank Soni, Priyanka Bhat
Although there is presence of a dense network of the cerebral vasculature, systemic delivery of therapeutics to the central nervous system (CNS) is infective for greater than 98% of small molecules and for nearly 100% of large molecules. This is imputable to the presence of the blood brain barrier (BBB), which prevents most foreign substances, even many beneficial therapeutics, from getting into the psyche from the systemic circulation. Certain small molecules, peptide, and protein therapeutics given systematically reach the brain parenchyma by crossing BBB but high systemic doses are required to reach a therapeutic level that contributes to adverse effects in the physical structure. The BBB is a system of layers of cells at the cerebral capillary endothelium, the choroid plexus epithelium, and the arachnoid membranes, which are linked by tight junctions (zonulae occludens) and which together separate the mind and the cerebro-spinal fluid (CSF) from the line. These tight endothelial junctions can be 100 times tighter than junctions of other capillary endothelium. Therefore, the barrier has many attributes similar to a continuous cell membrane, allowing lipid soluble molecule transport across the membrane where hydrophilic solutes demonstrate minimal permeation. Different strategies have been developed to cross the BBB have been involved, such as synthesis of small molecules to exploit existing Carrier-Mediated Transport (CMT) or re-engineering large molecules with molecular ‘Trojan horse’ delivery systems. These approaches may allow transport via Receptor-Mediated Transfer (RMT) systems in the BBB. An alternative approach is targeted intranasal delivery, which is potentially applicable which covers broader area of molecules, where the goal is to circumvent, rather than cross, the BBB.