Characteristics of compounds that cross the blood-brain barrier
Top Cited Papers
Open Access
- 1 January 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in BMC Neurology
- Vol. 9 (Suppl 1), S3
- https://doi.org/10.1186/1471-2377-9-s1-s3
Abstract
Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transporters, adsorptive endocytosis, and the extracellular pathways. Here, we focus on the chief characteristics of two mechanisms especially important in drug delivery: transmembrane diffusion and transporters. Transmembrane diffusion is non-saturable and depends, on first analysis, on the physicochemical characteristics of the substance. However, brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can greatly alter the amount of the substance crossing the BBB. Transport systems increase uptake of ligands by roughly 10-fold and are modified by physiological events and disease states. Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes for which transporters have been described in recent years. We discuss two examples of drug delivery for newly discovered transporters: that for phosphorothioate oligonucleotides and for enzymes.Keywords
This publication has 45 references indexed in Scilit:
- Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood–brain barrierPeptides, 2008
- Mannose 6-Phosphate Receptor–mediated Transport of Sulfamidase Across the Blood–brain Barrier in the Newborn MouseMolecular Therapy, 2008
- Starvation and Triglycerides Reverse the Obesity-Induced Impairment of Insulin Transport at the Blood-Brain BarrierEndocrinology, 2008
- Epinephrine enhances lysosomal enzyme delivery across the blood–brain barrier by up-regulation of the mannose 6-phosphate receptorProceedings of the National Academy of Sciences, 2007
- Mechanisms of the Blood–Brain Barrier Disruption in HIV-1 InfectionCellular and Molecular Neurobiology, 2005
- Intranasal insulin improves memory in humansPsychoneuroendocrinology, 2004
- The Impact of Efflux Transporters in the Brain on the Development of Drugs for CNS DisordersClinical Pharmacokinetics, 2002
- Regional transport of TNF-α across the blood-brain barrier in young ICR and young and aged SAMP8 miceNeurobiology of Aging, 2001
- Changing the chemokine gradient: CINC1 crosses the blood–brain barrierJournal of Neuroimmunology, 2001
- Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeabilityJournal of Medicinal Chemistry, 1980