Abstract
The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the bloodbrain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer addedvalue for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates.
Keywords: Choroid plexus, cerebrospinal fluid, cerebral drug delivery, receptor-mediated transcytosis, folate receptor, LRP proteins, transferrin receptor, insulin receptor.
Current Pharmaceutical Design
Title:Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Volume: 22 Issue: 35
Author(s): Nathalie Strazielle and Jean-François Ghersi-Egea
Affiliation:
Keywords: Choroid plexus, cerebrospinal fluid, cerebral drug delivery, receptor-mediated transcytosis, folate receptor, LRP proteins, transferrin receptor, insulin receptor.
Abstract: The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the bloodbrain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer addedvalue for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates.
Export Options
About this article
Cite this article as:
Strazielle Nathalie and Ghersi-Egea Jean-François, Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier, Current Pharmaceutical Design 2016; 22 (35) . https://dx.doi.org/10.2174/1381612822666160726112115
DOI https://dx.doi.org/10.2174/1381612822666160726112115 |
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
-
Iron Overload is Associated with Perihematoma Edema Growth Following Intracerebral Hemorrhage that may Contribute to In-hospital Mortality and Long-term Functional Outcome
Current Neurovascular Research Dysregulation of Neurotrophic and Haematopoietic Growth Factors in Alzheimer’s Disease: From Pathophysiology to Novel Treatment Strategies
Current Alzheimer Research Myotonic Dystrophies 1 and 2: Complex Diseases with Complex Mechanisms
Current Genomics BDNF Serum Concentrations Show No Relationship with Diagnostic Group or Medication Status in Neurodegenerative Disease
Current Alzheimer Research Case Series and Mini-Review on Elizabethkingia meningoseptica, A high Alert Organism Causing Meningitis in Premature Neonates from A Tertiary Care Hospital of Western Rajasthan
Infectious Disorders - Drug Targets Congenital Malformations Attributed to Prenatal Exposure to Cyclophosphamide
Anti-Cancer Agents in Medicinal Chemistry A Translational View of Peptide Treatment of Neurological Disorders
Current Medicinal Chemistry Clearance of Amyloid-β Peptide Across the Blood-Brain Barrier: Implication for Therapies in Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2
Current Drug Metabolism New Approaches in Nuclear Medicine for Early Diagnosis of Alzheimers Disease
Current Alzheimer Research Intracranial Cerebrospinal Fluid Volume Evaluation in Healthy People and Hydrocephalus Patients using SPACE Sequence
Current Medical Imaging Cerebral Hypoperfusion During Carotid Artery Stenosis can Lead to Cognitive Deficits that may be Independent of White Matter Lesion Load
Current Neurovascular Research Intrathecal Enzyme Replacement Therapy for Mucopolysaccharidosis I: Translating Success in Animal Models to Patients
Current Pharmaceutical Biotechnology Tuberculostatic Drugs Targeting Infections of the Central Nervous System
Anti-Infective Agents Novel Agents in CNS Myeloma Treatment
Central Nervous System Agents in Medicinal Chemistry Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-analysis
Current Alzheimer Research Functional Role of Lipoprotein Receptors in Alzheimers Disease
Current Alzheimer Research Stem Cell Genetic Therapy for Fanconi Anemia – A New Hope
Current Gene Therapy Noninvasive Monitoring of Intracranial Pressure
Recent Patents on Biomedical Engineering (Discontinued) Apo-E4 Allele in Conjunction with Aβ42 and Tau in CSF: Biomarker for Alzheimers Disease
Current Alzheimer Research