Partitioning and structural effects of the antitumor drug daunomycin on model membranes

The effects of the antitumor drug daunomycin on the phase transition and dynamic properties of phosphatidylcholine membranes were investigated using the electron paramagenetic resonance spin labeling method. Multilamellar liposomes made of saturated dimyristoylphosphatidylcholine and unsaturated egg yolk phosphatidylcholine were used. The main phase transition of saturated bilayer was significantly broadened in the presence of daunomycin. In the fluid phase of saturated membranes, daunomycin caused a decrease in the rotational motion of the spin probe 16-doxylstearic acid (16-SASL). This effect was strongly diminished by raising the temperature. In unsaturated membranes no influence of daunomycin on the rotational motion of 16-SASL was observed. It is proposed that the neutral form of daunomycin can partition into lipid bilayer where it can diffuse into deeper hydrophobic regions of the membrane and decrease the motion of alkyl chains.