Influence of cationic amphiphilic drugs on the phase-transition temperature of phospholipids with different polar headgroups

Abstract

The influence of a number of cationic amphiphilic drugs on the phase-transition temperature (T t) of liposomes prepared of dipalmitoylphosphatidic acid (DPPA) and of dipalmitoylphosphatidylglycerol (DPPG) was investigated applying the method of differential scanning calorimetry. Under control conditions, the transition from the gel to the liquid crystalline state occured in DPPA liposomes at T t≈63°C and in DPPG liposomes at T t≈42°C, the difference of 20 deg. C reflecting the specific influence of the phospholipid polar headgroups on T t. Addition of a drug to DPPA liposomes induced a second transition signal at a much lower temperature, indicating the presence of drug-containing DPPA domains. The temperature of the drug-induced transition was almost independent of the amount of drug added but differed according to the drug under investigation. In DPPG liposomes, the temperature of the control transition declined gradually depending on the amount of a drug added until all DPPG molecules were uniformly affected by drug molecules. The temperature of this drug-induced transition differed depending on the drug tested. A comparison revealed that the T t values induced by a given drug were similar in DPPA, DPPG and also DPPC liposomes in spite of the widely different T t values of these phospholipids under control conditions. It is concluded that the intercalation of drug molecules between the polar headgroups of the phospholipids almost eliminates the specific influence of the headgroups on the T t of the investigated phospholipids.