The priorities/needs of the pharmaceutical industry in drug delivery to the brain

Abstract

Drug accessibility to the central nervous system (CNS) is the limiting factor in CNS drug development because many drugs do not penetrate the brain sufficiently. The highly restrictive endothelium of the brain capillary bed, i.e., the blood–brain barrier (BBB), and the protective epithelial layer of the choroid plexus, i.e., the blood–cerebrospinal fluid barrier (BCSFB), represent insurmountable obstacles for the brain penetration of many pharmacologically active compounds. Early assessment of the ability of drug candidate to penetrate the CNS is critical and crucial during the drug discovery process. A number of in vitro and in vivo approaches are available to aid in compound profiling: in silico prediction of BBB permeation, in vitro models of BBB and BCSFB, in situ and in vivo methods. Each technique has its own application with specific advantages and limitations; the strategy used by pharmaceutical research should be a combination of different models in order to obtain the best predictability to the clinical situation. Following the identification of brain penetration characteristics and the selection of the most promising compounds, the success of a CNS drug development program may be increased by enhancing drug delivery to the CNS. Strategies for CNS drug delivery may be classified as being invasive, pharmaceutical and biochemical.