Drug Transport into the Mammalian Brain: The Nasal Pathway and its Specific Metabolic Barrier

It is generally accepted that the rate of entry into and distribution of drugs and other xenobiotics within the central nervous system (CNS) depends on the particular anatomy of the brain microvessels forming the blood-brain barrier (BBB), and of the choroid plexus forming the blood-cerebrospinal fl...

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Bibliographic Details
Published in:Journal of drug targeting 2002, Vol.10 (4), p.285-296
Main Authors: Minn, Alain, Leclerc, Séverine, Heydel, Jean-Marie, Minn, Anne-Laure, Denizot, Claire, Cattarelli, Martine, Netter, Patrick, Gradinaru, Daniela
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Biological Transport - drug effects
Biological Transport - physiology
Blood-brain Barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - physiology
Brain - metabolism
Drug Metabolism
Drug Transport
Humans
Nasal Cavity - drug effects
Nasal Cavity - metabolism
Olfactory Bulb
Olfactory Mucosa
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Summary:It is generally accepted that the rate of entry into and distribution of drugs and other xenobiotics within the central nervous system (CNS) depends on the particular anatomy of the brain microvessels forming the blood-brain barrier (BBB), and of the choroid plexus forming the blood-cerebrospinal fluid barrier (CSF), which possess tight junctions preventing the passage of most polar substances. Drug entry to the CNS also depends on the physicochemical properties of the substances, which can be metabolised during this transport to pharmacologically inactive, non-penetrating polar products. Finally, the entry of drugs may be prevented by multiple complex specialized carriers, which are able to catalyse the active transport of numerous drugs and xenobiotics out of the CNS. Nasal delivery is currently considered as an efficient tool for systemic administration of drugs that are poorly absorbed via the oral route, and increasing evidence suggests that numerous drugs and potentially toxic xenobiotics can reach the CNS by this route. This short review summarizes recent knowledge on factors controlling the nasal pathway, focusing on drug metabolising enzymes in olfactory mucosa, olfactory bulb and brain, which should constitute a CNS metabolic barrier.
ISSN:1061-186X
1029-2330
DOI:10.1080/713714452