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KMID : 0617320020110010288
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Journal of Pharmacetical Sceiences Ewha Womans University
2002 Volume.11 No. 1 p.288 ~ p.292
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Blood-Brain Barrier Disruption Following the Internal Carotid Arterial Perfusion of Alkyl Glycerols
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LEE, HWA JEONG
ZHANG, YUN/PARDRIDGE, WILLIAM M.
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Abstract
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Non ionic, amphipathic molecules form vesicles and this property correlates with the disruption ofmembranes. In the present studies, high mM concenrations of aliphatic alcohols.1-0-hexyldiglycerol(HDG) and 1-0-heptyltriglycerol (HTG), are shown to cause enhanced drug transport into brain viadisruption of the blood-brain barrier (BBB) in vivo, as determined with an internal carotid arteryperfusion method. The intravenous administration of comparable conceutrations of HDG or HTGcaused no increase in BBB transport of drug. The enhanced transport of drug showed a dependency ormolecular weight as 45 mM HTG increased the transport of sucrose,360Da, but did not increase thetransport of arginine vasopressin (AVP), 1084Da, although AVP transport across the BBB wasincreased by 80mM HDG or HTG. Ouasielastic light scattering measurements provided evidence forthe formation of vesicular structures in aqueous solutions containing high mM concentrations of theHDG or HTG. In summary, these studies demonstrate BBB disruptien following the infernal carotidauerial infusion of high mM concentrations of membrane active alkyl g1ycerols.
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KEYWORD
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