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Mechanisms of Drug Transport Across the Blood-Brain Barrier.

Applicant Drewe Jürgen
Number 52918
Funding scheme Project funding (Div. I-III)
Research institution Departement Anästhesie Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Pharmacology
Start/End 01.04.1998 - 30.09.2001
Approved amount 315'000.00
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Lay Summary (English)

Lead
Lay summary
An in vitro system of the blood-brain barrier consisting of primary cultures of brain capillary endothelial cells (BCEC) has been established and characterized. The mechanisms of uptake into and transport through monolayers of BCEC has been investigated for the peptide analogs benzylpenicillin and glycylsarcosine, for clonidine and for the analgeticagents morphine and morphine-6-glucuronide (M-6-G). Clonidine was shown to penetrate BCEC by a carrier-dependent mechanism. Uptake of peptide analogs and M-6-G were unexpectedly low. Brain penetration of M-6-G was shown to be modulated by P-glycoprotein, an ATP-dependent drug efflux pump. Due tothe broad substrate specificity of P-glycoprotein brain permeability and thus pharmacological action of other clinically relevant drugs may depend on expression of P-glycoprotein in brain capillary endothelial cells. These results have prompted us to investigate in more detail expression of P-glycoprotein in endothelia and epithelia and to explore immunoliposome-based drug delivery strategies.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
42179 Drug Transport Across the Blood-Brain Barrier. 01.04.1995 Project funding (Div. I-III)
133859 Purchase of a laser scanning microscope / LSM710 Carl Zeiss 01.12.2010 R'EQUIP

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