Alkylphospholipids are physiologically active derivatives of
lipids effective in the treatment of
breast cancer. Among them, octadecyl-(1,1-dimethyl-4-piperidino-4-yl)-phosphate (
OPP) was demonstrated recently to have the strongest antitumor effect in micellar as well as in sterically stabilised
liposome suspension with a low
cholesterol content. In this work electron paramagnetic resonance (EPR) was used to study the influence of
cholesterol, charge, and sterical stabilisation by PEG2000DSPE on the domain structure and fluidity characteristics of the membrane of
OPP liposomes. As a spin probe 5-doxylpalmitoyl methyl
ester was used. By computer simulation of the EPR spectra it was found that the experimental spectra are composed of three spectral components, which were attributed to three types of domains with different fluidity characteristics. The EPR parameters as well as the proportions of the individual domains were found to be mainly dependent on the amount of
cholesterol, and only to a minor degree on charge and sterical stabilisation. There was a pronounced increase in the proportion of membrane domains with low order parameter, when the molar ratio of
cholesterol to
OPP was decreased below 1. At the same time the order parameters of all domains decreased, pointing to a transition from a less to a more fluid membrane organisation. These results coincide with an improved therapeutic activity of formulations with a low molar ratio of
cholesterol to
OPP and indicates that the fluidity characteristics of the membrane may be important for the effectiveness of liposomal alkylphospholipids against
breast cancer cells.