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Furthermore, for the efficient transporter-mediated permeation across the BBB, the prodrugs must be able to bind also to the intracellular substrate binding site of the transporter at the abluminal membrane of the brain capillary endothelial cells and to be translocated out of the endothelial cells into the ECF and, subsequently, to the brain parenchyma through the targeted transporter (Figs

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