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 proteoli posomes entrapped in gel beads. The drug retention per phospholipid amount (the capacity factor K-s) reflects the drug partitioning. Cholesterol in th e bilayers decreased the K-s value and hence the partitioning into the memb rane 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 electrost atically with charged drugs to increase or decrease the drug partitioning i nto 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 K -s was fair for both liposomes and bacteriorhodopsin-cholesterol proteolipo somes. Detailed modeling of solute partitioning into biological membranes m ay require an extensive knowledge of their structures.