Influence of various cationic amphiphilic drugs on the phase-transition temperature of phosphatidylcholine liposomes

Abstract

The influence of 16 cationic amphiphilic compounds from various pharmacological groups on the phase-transition temperature (Tt) of dipalmitoyl-phosphatidylcholine (DPPC) liposomes was investigated using the method of differential scanning calorimetry. All drugs, the hydrophobicity of which varied in a wide range, depressed Tt. Biphasic dose-effect curves were obtained when the reduction of Tt (ΔTt) was plotted vs the molar ratio of drug/DPPC; beyond a plateau, Tt could again be reduced markedly by increasing the molar ratio. Concomitantly with the depression of Tt, the width of the transition peak changed in a characteristic way: it broadened during the (first) steep part of the dose-effect curves and became narrow like a control transition when the plateau of the dose-effect curves was reached. At still higher ratios the peak broadened again and eventually vanished, probably due to a detergent-like effect of the drug. Increasing hydrophobicity of the compounds shifted the dose-effect curves to lower molar ratios and enhanced the ΔTt, attained at the plateau phase. It is proposed that the different potencies of the drugs to depress Tt result from different binding equilibria between the compounds and DPPC membranes, the individual equilibrium being determined by hydrophobia attraction and electrostatic repulsion.