Drug Design, Development and Therapy (Oct 2019)
In-vitro blood-brain barrier models for drug screening and permeation studies: an overview
Abstract
Sounak Bagchi,1 Tanya Chhibber,1 Behnaz Lahooti,1 Angela Verma,1 Vivek Borse,2 Rahul Dev Jayant1 1Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA; 2Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, IndiaCorrespondence: Rahul Dev JayantDepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter Street, Suite 1104, Amarillo, TX 79106, USATel +1 806 414 9154Fax +1 806 356 4034Email [email protected]: The blood-brain barrier (BBB) is comprised of brain microvascular endothelial central nervous system (CNS) cells, which communicate with other CNS cells (astrocytes, pericytes) and behave according to the state of the CNS, by responding against pathological environments and modulating disease progression. The BBB plays a crucial role in maintaining homeostasis in the CNS by maintaining restricted transport of toxic or harmful molecules, transport of nutrients, and removal of metabolites from the brain. Neurological disorders, such as NeuroHIV, cerebral stroke, brain tumors, and other neurodegenerative diseases increase the permeability of the BBB. While on the other hand, semipermeable nature of BBB restricts the movement of bigger molecules i.e. drugs or proteins (>500 kDa) across it, leading to minimal bioavailability of drugs in the CNS. This poses the most significant shortcoming in the development of therapeutics for CNS neurodegenerative disorders. Although the complexity of the BBB (dynamic and adaptable barrier) affects approaches of CNS drug delivery and promotes disease progression, understanding the composition and functions of BBB provides a platform for novel innovative approaches towards drug delivery to CNS. The methodical and scientific interests in the physiology and pathology of the BBB led to the development and the advancement of numerous in vitro models of the BBB. This review discusses the fundamentals of BBB structure, permeation mechanisms, an overview of all the different in-vitro BBB models with their advantages and disadvantages, and rationale of selecting penetration prediction methods towards the critical role in the development of the CNS therapeutics.Keywords: blood-brain barrier, BBB, brain microvascular endothelial cells, BMECs, tight junctions, TJs, proteins, central nervous system, CNS, induced pluripotent cells, iPSCs, in-silico prediction methods
