Effect of phenothiazine derivatives on the thermotropic phase transition of liposomal phospholipid membrane

The effect of phenothiazine derivatives on the thermotropic transition of liposomal lipid bilayer made of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidic acid was investigated with differential scanning calorimetry. The thermograms of the liposomal bilayer incorporated with levomepromazine, chlorpromazine, prochlorperazine, perphenazine and fluphenazine were obtained and the size of cooperative unit of the transition were calculated from the ratio of the van’t Hoff enthalpy change to the calculated enthalpy change of the transition. The results showed that incorporation of phenothiazine derivatives into the liposomal bilayer reduced the transition temperature at which the transition from solid state to liquid-crystalline state occurs, and broadened the thermogram peaks. Phenothiazine derivatives also significantly reduced the size of cooperative unit of the transition. The effect of the drugs was proportional to the concentration of the drug in the bilayer. This means that phenothiazine derivatives might have significant fluidizing effects on the biomembrane. The sizes of cooperative unit were successfully correlated with pharmacological activities of the drugs and the surface pressure increases of lipid monolayer by these drugs. These correlations might be ascribed to a possible hydrophobic nature of interaction between the biomembrane and the drugs involved in their pharmacology.