ReviewClinical pharmacology and therapeutics2022
Understanding the Blood-Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics.
Review in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Do Brain Extracellular Fluid Concentrations Predict PET-Inferred Receptor Occupancy in Human CNS? A Mechanistic Model-Based Analysis of Dopamine D2 Receptor Ligands.Clinical pharmacology and therapeutics · 2026Article
- From Xenobiotic Exposure to Neuroinflammation: Mechanisms Linking Lipopolysaccharide Signaling to Depressive-like Behavior.Journal of xenobiotics · 2026Review
- Introduction to Single-cell Physiologically-Based Pharmacokinetic (scPBPK) Models.bioRxiv : the preprint server for biology · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Bioisostere-Driven Discovery of SePP: A Selenium-Containing Polypharmacological Agent Relevant to Fragile X Syndrome.Journal of medicinal chemistry · 2026Article
- Repurposing Imeglimin for Chemotherapy-Induced Cognitive Impairment: Targeting Mitochondrial Dysfunction and Neuroinflammation.Cellular and molecular neurobiology · 2026Review
- PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2026Article
- Targeting the Dectin-1 Receptor in Neuroinflammation: Therapeutic Implications for Neuropsychiatric Disorders.ACS chemical neuroscience · 2025Review
- Advancement in tumor treating fields of mechanism, clinical applications, and future directions.Discover oncology · 2025Review
- Acute inflammation induced by the Escherichia coli lipopolysaccharide considerably increases the systemic and brain exposure of olanzapine after oral administration in mice.The international journal of neuropsychopharmacology · 2025Article
- A Repurposed Drug Selection Pipeline to Identify CNS-Penetrant Drug Candidates for Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy.International journal of nanomedicine · 2024Review
- Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice.Pharmaceutical research · 2023Article
- Status of Metabolomic Measurement for Insights in Alzheimer's Disease Progression-What Is Missing?International journal of molecular sciences · 2023Review
- Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This review addresses questions on how to accomplish successful central nervous system (CNS) drug delivery (i.e., having the right concentration at the right CNS site, at the right time), by understanding the rate and extent of blood-brain barrier (BBB) transport and intra-CNS distribution in relation to CNS target site(s) exposure. To this end, we need to obtain and integrate quantitative and connected data on BBB using the Combinatory Mapping Approach that includes in vivo and ex vivo animal measurements, and the physiologically based comprehensive LEICNSPK3.0 mathematical model that can translate from animals to humans. For small molecules, slow diffusional BBB transport and active influx and efflux BBB transport determine the differences between plasma and CNS pharmacokinetics. Obviously, active efflux is important for limiting CNS drug delivery. Furthermore, liposomal formulations of small molecules may to a certain extent circumvent active influx and efflux at the BBB. Interestingly, for CNS pathologies, despite all reported disease associated BBB and CNS functional changes in animals and humans, integrative studies typically show a lack of changes on CNS drug delivery for the small molecules. In contrast, the understanding of the complex vesicle-based BBB transport modes that are important for CNS delivery of large molecules is in progress, and their BBB transport seems to be significantly affected by CNS diseases. In conclusion, today, CNS drug delivery of small drugs can be well assessed and understood by integrative approaches, although there is still quite a long way to go to understand CNS drug delivery of large molecules.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.