title: The blood-brain barrier: structure, function and therapeutic approaches to cross it.
abstract: The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.
authors.affiliation: Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF) , Barcelona, Spain .
authors.forename: Marta
authors.initials: M
authors.lastname: Tajes
authors.forename: Eva
authors.initials: E
authors.lastname: Ramos-Fernández
authors.forename: Xian
authors.initials: X
authors.lastname: Weng-Jiang
authors.forename: Mònica
authors.initials: M
authors.lastname: Bosch-Morató
authors.forename: Biuse
authors.initials: B
authors.lastname: Guivernau
authors.forename: Abel
authors.initials: A
authors.lastname: Eraso-Pichot
authors.forename: Bertrán
authors.initials: B
authors.lastname: Salvador
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernàndez-Busquets
authors.forename: Jaume
authors.initials: J
authors.lastname: Roquer
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Muñoz
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D001523:Mental Disorders / Q000188:drug therapy / Q000473:pathology; D036103:Nanotechnology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology
chemical_list: D008081:Liposomes
keywords: Blood brain barrier; drug delivery; membrane transport