Abstract
With the aging population the occurrence of central nervous system diseases such as cancer, mental disorders and neurodegenerative diseases, is expected to increase and hence, the demand for effective drugs. However, the passage of drugs across the blood-brain barrier represents a major challenge in accomplishing efficient brain delivery of therapeutic agents. This highly efficient barrier is composed of a monolayer of capillary endothelial cells supported by pericytes and astrocytic end-feet, that together effectively shield the brain from the blood. The brain microvascular endothelial cells form a physical and metabolic barrier where paracellular and transcellular transport of molecules in and out of the brain is closely regulated, allowing nutrients to pass but preventing the entry of harmful neurotoxic substances, including drugs. For this purpose brain endothelial cells express efficient efflux pumps, such as ATP binding cassette (ABC) transporters, which limit the delivery of drugs into the brain. To treat the above-mentioned chronic central nervous system disorders, it is crucial to design compounds that can pass the blood-brain barrier and thus the ABC transporters. In order to achieve this, representative models of the blood-brain barrier with predictive validity are necessary. This review discusses the current in vitro and ex vivo model systems that are used to measure ABC transporter activity in order to study potential in vivo efficacy of blood-brain barrier-drug passage.
Keywords: Blood-brain barrier, ABC transporters, drug delivery, P-glycoprotein, breast cancer resistant protein, central nervous system diseases.
Current Pharmaceutical Design
Title:In Vitro and Ex Vivo Model Systems to Measure ABC Transporter Activity at the Blood-Brain Barrier
Volume: 22 Issue: 38
Author(s): Nienke M. de Wit, Gijs Kooij and Helga E. de Vries
Affiliation:
Keywords: Blood-brain barrier, ABC transporters, drug delivery, P-glycoprotein, breast cancer resistant protein, central nervous system diseases.
Abstract: With the aging population the occurrence of central nervous system diseases such as cancer, mental disorders and neurodegenerative diseases, is expected to increase and hence, the demand for effective drugs. However, the passage of drugs across the blood-brain barrier represents a major challenge in accomplishing efficient brain delivery of therapeutic agents. This highly efficient barrier is composed of a monolayer of capillary endothelial cells supported by pericytes and astrocytic end-feet, that together effectively shield the brain from the blood. The brain microvascular endothelial cells form a physical and metabolic barrier where paracellular and transcellular transport of molecules in and out of the brain is closely regulated, allowing nutrients to pass but preventing the entry of harmful neurotoxic substances, including drugs. For this purpose brain endothelial cells express efficient efflux pumps, such as ATP binding cassette (ABC) transporters, which limit the delivery of drugs into the brain. To treat the above-mentioned chronic central nervous system disorders, it is crucial to design compounds that can pass the blood-brain barrier and thus the ABC transporters. In order to achieve this, representative models of the blood-brain barrier with predictive validity are necessary. This review discusses the current in vitro and ex vivo model systems that are used to measure ABC transporter activity in order to study potential in vivo efficacy of blood-brain barrier-drug passage.
Export Options
About this article
Cite this article as:
Wit M. de Nienke, Kooij Gijs and Vries E. de Helga, In Vitro and Ex Vivo Model Systems to Measure ABC Transporter Activity at the Blood-Brain Barrier, Current Pharmaceutical Design 2016; 22 (38) . https://dx.doi.org/10.2174/1381612822666160810145536
DOI https://dx.doi.org/10.2174/1381612822666160810145536 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Preface [Hot topic: Autoimmunity (Executive Editors: D. Stahl and W. Sibrowski)]
Current Pharmaceutical Design Immunomodulatory Lactoferrin in the Regulation of Apoptosis Modulatory Proteins in Cancer
Protein & Peptide Letters Genetic Studies of Type 2 Diabetes in South Asians: A Systematic Overview
Current Diabetes Reviews Editorial [Hot Topic: Clinical Trials in ANCA Associated Vasculitis (Guest Editor: Chetan Mukhtyar)]
Current Immunology Reviews (Discontinued) Pharmacogenetically Tailored Treatments for Heart Disease
Current Pharmaceutical Design Emerging Treatment Strategies and Potential Therapeutic Targets in Primary Sjogrens Syndrome
Inflammation & Allergy - Drug Targets (Discontinued) microRNAs: Promising Biomarkers and Therapeutic Targets of Acute Myocardial Ischemia
Current Vascular Pharmacology Pattern of Primary Vasculitis with Peripheral Ischemic Manifestations: Report of a Case Series and Role of Vascular Surgery
Current Rheumatology Reviews Long-Term Extensions of Randomized Vaccination Trials of ACC-001 and QS-21 in Mild to Moderate Alzheimer’s Disease
Current Alzheimer Research RAGE Signaling in Cell Adhesion and Inflammation
Current Pediatric Reviews Activation of the Liver X Receptor Inhibits Th17 and Th1 Responses in Behcet`s Disease and Vogt-Koyanagi-Harada Disease
Current Molecular Medicine Targeting the Endothelial Ca2+ Toolkit to Rescue Endothelial Dysfunction in Obesity Associated-Hypertension
Current Medicinal Chemistry Chronic Inflammation and Colorectal Cancer: The Role of Vascular Endothelial Growth Factor
Current Pharmaceutical Design Autoimmune Diseases and Atherosclerosis: The Inflammatory Connection
Current Immunology Reviews (Discontinued) Insulin-Degrading Enzyme: Structure-Function Relationship and its Possible Roles in Health and Disease
Current Pharmaceutical Design Pathophysiology of Atherosclerosis: The Role of Inflammation
Current Pharmaceutical Design Effect of an Angiotensin II Receptor Blocker and Two Angiotensin Converting Enzyme Inhibitors on Transforming Growth Factor-β (TGF-β) and α-Actomyosin (α SMA), Important Mediators of Radiation-Induced Pneumopathy and Lung Fibrosis
Current Pharmaceutical Design Therapeutic Potential of Targeting TREM-1 in Inflammatory Diseases and Cancer
Current Pharmaceutical Design Current Update on Eosinophilic Lung Diseases and Anti-IL-5 Treatment
Recent Patents on Anti-Infective Drug Discovery Overlooked Issues of Snakebite Management: Time for Strategic Approach
Current Topics in Medicinal Chemistry