Investigating drug-liposome interactions using liposomal electrokinetic chromatography.

Abstract

This study explores the potential of using liposomal electrokinetic chromatography as a ranking method for the rapid and simultaneous evaluation of drug-membrane interactions of a larger group of substances and assessing their sensitivity to tissue-specific parameters, namely pH, temperature, and lipid composition. We used a group of nine model drug substances to manifest how molecules could be classified for the relative sensitivity of drug-membrane interactions to pH and temperature. We observed that increasing the amount of liposomes in the background electrolyte significantly affected the separation kinetics of various active pharmaceutical ingredients, altering their mobility and/or peak shapes. Experiments with liposomes from bovine liver and heart tissue extracts revealed different interactions based on the lipid composition. Canagliflozin, which initially showed no electrophoretic mobility, migrated toward the anode in the presence of negatively charged liposomes. Mobility of positively charged substances, ambroxol and maraviroc, was suppressed by the interactions with liposomes. Their peaks also exhibited significant tailing. The effect on the separation of negatively charged compounds was significantly weaker. A small change in mobility was observed only in the case of deferasirox. We also examined the effect of temperature during separation, and we observed that increased temperature generally enhanced effective mobility due to lower electrolyte viscosity and increased lipid bilayer fluidity. Lastly, we tested the effect of sodium phosphate buffer pH (ranging from 6.0 to 8.0) with 4% liposomes on drug-liposome interactions. However, the effects were complex due to changes in API ionization and liposome surface charge, complicating the distinction between pH effects and liposome presence on API behavior. Our findings emphasize the significance of liposome composition, temperature, and pH in studying the interactions of liposomes with drugs, which is crucial for optimizing liposome-based drug delivery systems.