Figure 1.

Schematic representation of the blood–brain barrier.

Notes: (A) Scheme of the neurovascular unit that constitutes the BBB. This unit contains the pericytes and astrocytes, which play an important role in the formation and differentiation of the CNS vasculature. (B) The main routes of the crossing of molecules to the CNS are represented. (a) A representation of the tight junctions severely restricting the penetration of water-soluble compounds, including polar drugs. (b) The endothelium contains transport proteins (carriers) for glucose, amino acids, purine bases, nucleosides, choline, and other substances. Some transporters are energy dependent (eg, P-glycoprotein) and act as efflux transporters (eg, azidothymidine). (c) An effective diffusive route for lipid-soluble agents to cross the membranes of the endothelium. (d) Certain proteins, such as insulin and transferrin, are taken up by specific receptor-mediated endocytosis and transcytosis. Nanoparticles capped with these molecules can cross the BBB. (e) Native plasma proteins such as albumin are poorly transported; however, cationization can increase their uptake by adsorptive-mediated endocytosis and transcytosis. (f) The efflux pump expulses the drugs from the endothelial cells to the blood. Delivery of nanoparticles across the brain endothelium enters mainly via routes (d) and (e). (g) Cytochrome P450 enzymes. Adapted from Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.²²

Abbreviations: BBB, blood–brain barrier; CNS, central nervous system.