Investigations of Liposome/Water Partitioning Using Electrokinetic Chromatography

Abstract

In this two-part investigation, Linear Solvation Energy Relationship (LSER) models were applied to liposome/water partitioning data determined by liposome electrokinetic chromatography (LEKC). In the first part of the study, LEKC retention factors were determined for a set of 71 solutes including 50 neutral aromatic solutes and 21 neutral drugs using the liposome phases mM DPPG20DPPC80, 15 mM DPPG20DPPC80/3 mM cholesterol, and 15 mM DPPG20DPPC80/6 mM cholesterol. These retention factors were used to determine linear solvation energy relationships (LSER) models for each of the three lipid phases for the set of 50 neutral aromatic solutes and the entire set of 71 solutes. The predictive ability of the LSER model was tested by using the model generated for the set of 50 neutral aromatic solutes to predict retention factors for the 21 neutral drugs. The descriptive ability of the LSER model was tested and used to examine the interactions that control liposome/water partitioning for the set of 50 neutral aromatic solutes and the set of 71 solutes including 21 neutral drugs. In the second part of the study, wo liposome electrokinetic chromatography (LEKC) lipid phases were introduced that approximate the lipid composition of the cell membrane of monkey intestinal epithelial cells. 15 mM PI10DPPS10DPPC30DPPE30SPM20/9.75 mM cholesterol most nearly approximates the lipid composition of the cell membrane of monkey intestinal epithelial cells. 15 mM DPPG20DPPC80/9.75 mM cholesterol replaces the specific lipids contained in the monkey intestinal epithelial cell membranes with the zwitterioninc lipid DPPC and DPPG. The retention factors determined for a set of 50 neutral aromatic solutes using these two LEKC phases are highly correlated (r2=0.99), with a slope near unity (m=0.91) and an intercept near zero (b=0.05). The normalized LSER system coefficients for these lipid phases are also very similar. The LSER system coefficients determined for 15 mM PI10DPPS10DPPC30DPPE30SPM20/9.75 mM cholesterol and 15 mM DPPG20DPPC80/9.75 mM cholesterol were compared with an LSER model generated by Abraham, et al. for human intestinal absorption.