Immobilized liposome chromatography of drugs for model analysis of drug-membrane interactions

Liposomes are composed of lipid bilayers surrounding aqueous compartments. For attempts to predict drug absorption through cell membranes by use of a chromatographic model system, liposomes or biological membrane vesicles can be sterically immobilized by entrapment in the pores of gel beads upon freeze-thaw fusion of small liposomes or vesicles. Alternatively hydrophobic ligands attached to the gel matrix can be used for immobilization. The chromatographic retention of a drug on a gel bed containing a known amount of liposomes or membrane vesicles reveals the degree of interaction between the drug and the lipid bilayers, after correction for drug-gel matrix interaction. The experiments are performed in aqueous buffer and the stability of liposome immobilization allows series of runs over periods of several weeks. Liposomal lipid composition and surface charge affect the interaction. The specific capacity factors of several drugs correlate reasonably well with drug permeability through Caco-2 epithelial cell monolayers and with absorption of orally administered doses in humans.