<p>In-vitro blood-brain barrier models for drug screening and permeation studies: an overview</p>

Abstract

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.

In vitro modeling of the neurovascular unit: advances in the field

“…The unique advantage of using iPSCs is their ability to generate a representative model of patients from which they have been originated [140]. Additionally, recent advances in gene editing techniques provide exciting opportunities in disease modeling using iPSCs, although these methods still have hindrances like epigenetic reprogramming and loss of patient-specific epigenetic signature [141]. iPSCs technology has some major limitations so that the risk of tumor formation is present due to the use of viral infections and low efficiency of reprogramming during the production of these cells.…”

Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models

“…With the increasing concern of traumatic brain injuries, neurodegenerative diseases, and brain tumors, the progress of new therapies designed for central nervous system (CNS) illnesses is crucial for ensuring social and economic sustainability in an ageing world. In this line, tissue-engineered models could enable the study of clinically relevant processes such as CNS drug delivery efficiency through the blood-brain barrier (BBB) [4,5]. The BBB is a dynamic and complex structure of brain capillaries that tightly regulates the exchange of nutrients, oxygen, and metabolites between the circulating blood and the extracellular fluids of the nervous tissue in the CNS.…”

“…The BBB is essential for the control of CNS homeostasis and for the protection of the nervous tissue from toxins or pathogens, and alterations of this barrier underlie the progression of different neurological disorders. However, the BBB represents a critical hurdle in the treatment of CNS diseases as it prevents most pharmaceutical drugs from entering the brain due to its physical, biochemical, and specific barrier properties [5,6]. Interestingly, some neurotransmitters such as dopamine and serotonin involved in the physiopathology of the Parkinson and depression, respectively, cannot cross the BBB; in contrast, some of their precursors can cross this barrier and are used instead to treat these diseases [7].…”

Local Quantum Energy Conditions in Non-Lorentz-Invariant Quantum Field Theories

“…This will be particularly interesting for appearances of bms 3 symmetries beyond flat space holography such as tensionless bosonic string theory, see e.g. [17,66,67].…”