INTERACTIONS OF DRUGS WITH LIPID-MEMBRANES - CHARACTERISTICS OF LIPOSOMES CONTAINING POLAR OR NONPOLAR ANTI-TUMOR DRUGS

Polar drugs entrapped within liposomes are found in the internal aqueous compartments of these particles, and are readily released when the liposome membrane is ruptured by ultrasonic energy. Non-polar drugs are found or intercalated into the liposome membrane as well as being found in the aqueous compartments. The intercalated fraction of the non-polar drug is relatively refractory to release by ultrasonic energy. The efflux rates of both polar adn non-polar drugs from liposomes are governed by the physical characteristics of the liposome membrane. Thus drug efflux from liposomes composed of synthetic phosphatidylcholines displays a maximal rate at the phase transition temperature of the lipid. The efflux rate of non-polar drugs from phosphatidylcholine liposomes is greater than that of polar drugs. Non-polar drugs can perturb the phase transition behavior of synthetic phosphatidylcholines; polar drugs have no such effect. Thus, in the presence of non-polar drugs such as vinblastine sulfate and actinomycin D, the differential scanning calorimetry profile of dimyristoylphosphatidylcholine is markedly altered, with a broadening of the major peak and the appearance of a second peak at lower temperature. © 1979.