Immobilized-liposome chromatographic analysis of drug partitioning into lipid bilayers.

The chromatographic retardation of drugs on a gel bed with immobilized liposomes was shown to correlate with the absorption of the drugs through epithelial cell layers, which is related to drug partitioning into the lipid bilayers of cell membranes. The capacity factors were divided by the lipid concentration (mM) in the gel bed to obtain specific capacity factors, Ks. The logarithm of the octanol-water distribution ratios showed a linear correlation with log Ks, whereas the logarithm of the apparent permeability coefficients in epithelial cell monolayers and the absorption of drugs orally administered in humans (data from other laboratories) increased over the interval 0 < log Ks < 1 and attained a saturation level in the interval 1 < log Ks < 3. Immobilized-liposome chromatography may be applicable for prediction of drug uptake through epithelial cell membranes.

[1]  Q. Yang,et al.  Immobilization of phospholipid vesicles and protein-lipid vesicles containing red cell membrane proteins on octyl derivatives of large-pore gels. , 1988, Biochimica et biophysica acta.

[2]  G. Betageri,et al.  Thermodynamics of partitioning of β-blockers in the n-octanol- buffer and liposome systems , 1987 .

[3]  P. Artursson,et al.  Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. , 1991, Biochemical and biophysical research communications.

[4]  Q. Yang,et al.  Liposome chromatography: liposomes immobilized in gel beads as a stationary phase for aqueous column chromatography. , 1991, Journal of chromatography.

[5]  Aalt Bast,et al.  Comprehensive medicinal chemistry , 1991 .

[6]  G. R. Bartlett.  Phosphorus assay in column chromatography. , 1959, The Journal of biological chemistry.

[7]  I. Wainer,et al.  Deactivated hydrocarbonaceous silica and immobilized artificial membrane stationary phases in high-performance liquid chromatographic determination of hydrophobicities of organic bases: relationship to log P and CLOGP. , 1993, Journal of pharmaceutical and biomedical analysis.

[8]  G. Betageri,et al.  Partitioning and thermodynamics of dipyridamole in the n‐octanol/buffer and liposome systems , 1993, The Journal of pharmacy and pharmacology.

[9]  T. T. Ngo.  Molecular Interactions in Bioseparations , 1993, Springer US.

[10]  P. Artursson,et al.  Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. , 1990, Journal of pharmaceutical sciences.

[11]  J. Rogers,et al.  The temperature dependence and thermodynamics of partitioning of phenols in the n-octanol-water system , 1980 .

[12]  R. Kaliszan.  High Performance Liquid Chromatographic Methods and Procedures of Hydrophobicity Determination , 1990 .

[13]  Q. Yang,et al.  Steric immobilization of liposomes in chromatographic gel beads and incorporation of integral membrane proteins into their lipid bilayers. , 1994, Analytical biochemistry.

[14]  E. Brekkan,et al.  Effects of pH on the activity of the human red cell glucose transporter Glut 1: transport retention chromatography of D-glucose and L-glucose on immobilized Glut 1 liposomes. , 1993, Biochimica et biophysica acta.