Investigations of lipid phase/water partitioning using electrokinetic chromatography

The main goal of this research progress was to investigate different aspects of liposome/water partitioning using liposome electrokinetic chromatography (LEKC) with various lipid bilayer membrane pseudostationary phases and a wide variety of different test solutes.; The predictive and descriptive abilities of Linear Solvation Energy Relationships (LSER) models were used extensively over the course of this research project. The predictive ability of the LSER model was first tested by comparing experimental retention factors with retention factors predicted using LSER models determined using a set of simple test molecules for a set of neutral drugs. Later in the study, a similar approach was used to predict retention factors for aliphatic compounds that cannot be detected using UV absorbance. The descriptive ability was used to study the interactions that control liposome/water partitioning and to compare the selectivity of lipid phases of varied compositions. LSER models describing liposome/water partitioning behavior were also compared to those describing different biological processes such as intestinal and skin permeability.; The use of pseudostationary phases comprised of spontaneous unilamellar vesicles formed by the mixing of short-chain and long-chain lipids was also investigated. The sizes of these vesicles was characterized using dynamic light scattering and retention properties were characterized using a set of 50 test solutes. The temperature dependence and thermodynamic parameters of vesicle/water partitioning for these lipid phases were studied by fitting partition coefficients determined over a range of temperatures to nonlinear van't Hoff plats.; Finally, a quantative structure activity relationship (QSAR) was developed to predict skin permeability coefficients using LEKC retention factors, molecular weight, and a descriptor of hydrogen bonding determined using the solute structure. This model was favorably compared with other models used for the prediction of skin permeability coefficients using similar descriptors.