title: In vitro screening of nanomedicines through the blood brain barrier: A critical review.
abstract: The blood-brain barrier accounts for the high attrition rate of the treatments of most brain disorders, which therefore remain one of the greatest health-care challenges of the twenty first century. Against this background of hindrance to brain delivery, nanomedicine takes advantage of the assembly at the nanoscale of available biomaterials to provide a delivery platform with potential to raising brain levels of either imaging or therapeutic agents. Nevertheless, to prevent later failure due to ineffective drug levels at the target site, researchers have been endeavoring to develop a battery of in vitro screening procedures that can predict earlier in the drug discovery process the ability of these cutting-edge drug delivery platforms to cross the blood-brain barrier for biomedical purposes. This review provides an in-depth analysis of the currently available in vitro blood-brain barrier models (both cell-based and non-cell-based) with the focus on their suitability for understanding the biological brain distribution of forthcoming nanomedicines. The relationship between experimental factors and underlying physiological assumptions that would ultimately lead to a more predictive capacity of their in vivo performance, and those methods already assayed for the evaluation of the brain distribution of nanomedicines are comprehensively discussed.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Aparicio-Blanco
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martín-Sabroso
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain; University Institute of Industrial Pharmacy, Complutense University, 28040, Madrid, Spain. Electronic address: galaaaa@ucm.es.
authors.forename: Ana-Isabel
authors.initials: AI
authors.lastname: Torres-Suárez
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001812:Blood-Brain Barrier / Q000737:chemistry*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D053769:Nanocapsules
keywords: Brain targeting; Cell culture; Central nervous system; In vitro blood-brain barrier model; Nanomedicine; Parallel artificial membrane permeability assay