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Factors affecting delivery of antiviral drugs to the brain
Author(s) -
Strazielle Nathalie,
GhersiEgea JeanFrançois
Publication year - 2005
Publication title -
reviews in medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.06
H-Index - 90
eISSN - 1099-1654
pISSN - 1052-9276
DOI - 10.1002/rmv.454
Subject(s) - choroid plexus , blood–brain barrier , paracellular transport , cerebrospinal fluid , lipophilicity , drug delivery , polar surface area , pharmacology , bioavailability , tight junction , drug , biology , microvesicles , p glycoprotein , central nervous system , immunology , neuroscience , microbiology and biotechnology , chemistry , microrna , drug resistance , biochemistry , multiple drug resistance , permeability (electromagnetism) , organic chemistry , membrane , molecule , gene
Abstract Although the CNS is in part protected from peripheral insults by the blood–brain barrier and the blood‐cerebrospinal fluid barrier, a number of human viruses gain access to the brain, replicate within this organ, or sustain latent infection. The efficacy of antiviral drugs towards the cerebral viral load is often limited as both blood–brain interfaces impede their cerebral distribution. For polar compounds, the major factor restricting their entry lies in the tight junctions that occlude the paracellular pathway across these barriers. For compounds with more favourable lipid solubility properties, CNS penetration will be function of a number of physicochemical factors that include the degree of lipophilicity, size and ability to bind to protein or red blood cells, as well as other factors inherent to the vascular and choroidal systems, such as the local cerebral blood flow and the surface area available for exchange. In addition, influx and efflux transport systems, or metabolic processes active in both capillary endothelial cells and choroid plexus epithelial cells, can greatly change the bioavailability of a drug in one or several compartments of the CNS. The relative importance of these various factors with respect to the CNS delivery of the different classes of antiviral drugs is illustrated and discussed. Copyright © 2004 John Wiley & Sons, Ltd.