New experimental models of the blood-brain barrier for CNS drug discovery

Expert Opin Drug Discov. 2017 Jan;12(1):89-103. doi: 10.1080/17460441.2017.1253676. Epub 2016 Nov 7.

Abstract

The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered: This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies. Additionally, the authors laid out a roadmap for the integration of microfluidics and stem cell biology as a holistic approach for the development of novel in vitro BBB platforms. Expert opinion: Development of effective CNS drugs has been hindered by the lack of reliable strategies to mimic the BBB and cerebrovascular impairments in vitro. Technological advancements in BBB modeling have fostered the development of highly integrative and quasi- physiological in vitro platforms to support the process of drug discovery. These advanced in vitro tools are likely to further current understanding of the cerebrovascular modulatory mechanisms.

Keywords: In vitro; alternative; brain; brain disorders; cell culture; cerebrovascular; drug testing; permeability; technology.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain / metabolism
  • Central Nervous System Agents / pharmacokinetics
  • Central Nervous System Agents / pharmacology*
  • Central Nervous System Diseases / drug therapy
  • Drug Delivery Systems
  • Drug Discovery / methods
  • Humans
  • Microfluidic Analytical Techniques
  • Models, Biological*
  • Printing, Three-Dimensional
  • Stem Cells / cytology

Substances

  • Central Nervous System Agents