https://orcid.org/0009-0004-0344-2100
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ABSTRACT
Introduction
The efficiency of brain therapeutics is greatly hindered by the blood-brain barrier (BBB). BBB’s protective function, selective permeability, and dynamic functionality maintain the harmony between the brain and peripheral region. Thus, the design of any novel drug carrier system requires the complete study and investigation of BBB permeability, efflux transport, and the effect of associated cellular and non-vascular unit trafficking on BBB penetrability. The in vitro BBB models offer a most promising, and reliable mode of initial investigation of BBB permeability and associated factors as strong evidence for further preclinical and clinical investigation.
Area covered
This review work covers the structure and functions of BBB components and different types of in vitro BBB models along with factors affecting BBB model development and model selection criteria.
Expert opinion
In vivo models assume to reciprocate the physiological environment to the maximum extent. However, the interspecies variability, NVUs trafficking, dynamic behavior of BBB, etc., lead to non-reproducible results. The in vitro models are comparatively less complex, and flexible, as per the study design, could generate substantial evidence and help identify suitable in vivo animal model selection.
Article highlights
The co-culture BBB model can study the effect of different cellular components on BBB permeability.
Stem cell-derived BBB model can imitate the tight junction, TEER, and other transmembrane proteins.
The diseased BBB model can be used to study the target activation and altered permeability.
Organoid, spheroid, or hydrogel-based 3D BBB models replicate multiple components and the dynamic nature of BBB.
This box summarizes key points contained in the article.
Abbreviations
| BBB | = | Blood-Brain barrier |
| TEER | = | Trans endothelial electrical resistance |
| JAM | = | Junction adhesion molecule |
| EC | = | Endothelial Cells |
| NVU | = | Neuro Vascular Unit |
| hBECs | = | human Brain Endothelial Cells |
| CSF | = | Cerebrospinal Fluid |
| DIV-BBB | = | Dynamic in vitro BBB |
| BCEC | = | Brain capillary endothelial cells |
| BMECs | = | Brain microvascular endothelial cells |
| IRB | = | Institutional review board |
| CPF | = | Chlorpyrifos |
| PMT | = | Permethrin |
| CFT | = | Cyfluthrin |
| TJ | = | Tight Junction |
| ZO | = | Zonula occludens |
| QSAR | = | Quantitative Structural Activity Relationship |
| IVIVC | = | in vitro-in vivo correlation |
| P-gp | = | P-glycoprotein |
| HiPSCs | = | Human-induced Pluripotent Stem Cells |
| hPSCs | = | Human pluripotent stem cells |
| PECAM-1 | = | Platelet endothelial cell adhesion molecule |
| VE | = | vascular endothelial |
| hESC | = | human embryonic stem cell |
| vWF | = | von Willebrand factor |
| CAA | = | Cerebral Amyloid Angiopathy |
| IECs | = | Immortalized Endothelial Cells |
| BCRP | = | Breast Cancer Resistant Protein |
| OGD | = | Oxygen-Glucose Deprivation |
| BEC | = | Brain Endothelial Cells |
| iPSCs | = | induced Pluripotent Stem Cells |
| ESCs | = | Embryonic Stem Cells |
| RA | = | Retinoic Acid |
| PCR | = | Polymerase Chain Reaction |
| HTS | = | High Throughput Screening |
| BVOs | = | Blood Vessel Organoid |
| VEGF | = | Vascular endothelial Growth Factor |
| GBM | = | Glioblastoma multiforme |
| PDMS | = | Polydimethylsiloxane |
| PMMA | = | Poly(methylmethacrylate) |
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or the material discussed in the manuscript. This includes employment, consultancies, honorary, stock ownership or options, expert testimony, grants, patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
The author wants to extend gratitude to National Institute of Pharmaceutical Education and Research, Guwahati, India, for providing necessary support for compilation of this work.