Effects of cholesterol and model transmembrane proteins on drug partitioning into lipid bilayers as analysed by immobilized-liposome chromatography

We have analysed how cholesterol and transmembrane proteins in phospholipid bilayers modulate drug partitioning into the bilayers. For this purpose we determined the chromatographic retention of drugs on liposomes or proteoliposomes entrapped in gel beads. The drug retention per phospholipid amount...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2001-11, Vol.53 (11), p.1477-1487
Main Authors: Lagerquist, Caroline, Beigi, Farideh, Karlén, Anders, Lennernäs, Hans, Lundahl, Per
Format: Article
Language:English
Subjects:
Bacteriorhodopsins - chemistry
Cholesterol - chemistry
Chromatography - methods
Lipid Bilayers - chemistry
Liposomes - chemistry
Membrane Proteins - chemistry
Monosaccharide Transport Proteins - chemistry
Pharmaceutical Preparations - chemistry
Phospholipids - chemistry
Temperature
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Summary:We have analysed how cholesterol and transmembrane proteins in phospholipid bilayers modulate drug partitioning into the bilayers. For this purpose we determined the chromatographic retention of drugs on liposomes or proteoliposomes entrapped in gel beads. The drug retention per phospholipid amount (the capacity factor Ks) reflects the drug partitioning. Cholesterol in the bilayers decreased the Ks value and hence the partitioning into the membrane in proportion to the cholesterol fraction. On average this cholesterol effect decreased with increasing temperature. Model transmembrane proteins, the glucose transporter GLUT1 and bacteriorhodopsin, interacted electrostatically with charged drugs to increase or decrease the drug partitioning into the bilayers. Bacteriorhodopsin proteoliposomes containing cholesterol combined the effects of the protein and the cholesterol and approached the partitioning properties of red blood cell membranes. For positively charged drugs the correlation between calculated intestinal permeability and log Ks was fair for both liposomes and bacteriorhodopsin‐cholesterol proteoliposomes. Detailed modeling of solute partitioning into biological membranes may require an extensive knowledge of their structures.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357011778016