Strategies to Improve Drug Delivery Across the Blood-Brain Barrier
- 1 January 2007
- journal article
- review article
- Published by Springer Nature in Clinical Pharmacokinetics
- Vol. 46 (7) , 553-576
- https://doi.org/10.2165/00003088-200746070-00002
Abstract
The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.Keywords
This publication has 179 references indexed in Scilit:
- Effect of cationic carriers on the pharmacokinetics and tumor localization of nucleic acids after intravenous administrationInternational Journal of Pharmaceutics, 2007
- Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexesJournal of Controlled Release, 2006
- Targeted delivery of antibodies through the blood–brain barrier by MRI-guided focused ultrasoundBiochemical and Biophysical Research Communications, 2006
- Brain Endothelial Hemostasis Regulation by PericytesJournal of Cerebral Blood Flow & Metabolism, 2005
- Sequential Injection of Cationic Liposome and Plasmid DNA Effectively Transfects the Lung with Minimal Inflammatory ToxicityMolecular Therapy, 2001
- Glycoprotein 330/Megalin (LRP-2) Has Low Prevalence as mRNA and Protein in Brain Microvessels and Choroid PlexusExperimental Neurology, 1999
- Regional distribution of heparin-binding epidermal growth factor-like growth factor mRNA and protein in adult rat forebrainNeuroscience Letters, 1996
- Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.Journal of Clinical Investigation, 1995
- A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the ratDevelopmental Brain Research, 1990
- Ultracytochemical characterization of anionic sites in the wall of brain capillariesJournal of Neurocytology, 1989