Molecular determinants of blood-brain barrier permeation.

Molecular determinants of blood-brain barrier permeation.

Geldenhuys Werner J; Mohammad Afroz S; Adkins Chris E; Lockman Paul R

Therapeutic delivery

2015

1905-7

The blood-brain barrier (BBB) is a microvascular unit which selectively regulates the permeability of drugs to the brain. With the rise in CNS drug targets and diseases, there is a need to be able to accurately predict a priori which compounds in a company database should be pursued for favorable properties. In this review, we will explore the different computational tools available today, as well as underpin these to the experimental methods used to determine BBB permeability. These include in vitro models and the in vivo models that yield the dataset we use to generate predictive models. Understanding of how these models were experimentally derived determines our accurate and predicted use for determining a balance between activity and BBB distribution.

Humans; Animals; *Drug Delivery Systems; Blood-Brain Barrier/*metabolism; Brain/drug effects; Computer Simulation; high-throughput; in silico; logPS; nutrient transporters; Permeability; virtual screening

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

961–971

8

6