Adsorption of the cationic antitumoral drug celiptium to phosphatidylglycerol in membrane model systems. Effect on membrane electrical properties

The binding of the cationic antitumoral drug Celiptium to the anionic phospholipid phosphatidylglycerol was studied by measuring surface potentials and surface pressures in monolayers, and by determination of electrophoretic mobility on liposomes. Surface potential and zeta potential data were interpreted in terms of the Gouy-Chapman-Stern theory of the diffuse electrical double layer. A unique drug-to-lipid adsorption constant KaD, could not be calculated. KaD was observed to increase rapidly from 10(4) M-1 to 10(6) M-1 with an increase in drug concentration from 5 x 10(-7) M to 7 x 10(-6) M. This was accompanied by a marked decrease (in absolute value) in the corresponding electrophoretic mobilities which, from negative at low drug concentrations, became positive at drug concentrations of 10(-5) M and above. This indicates that the drug-to-lipid binding cannot be accounted for by a simple Langmuir adsorption isotherm, but corresponds to a more complex process, probably of a cooperative nature. Comparison of delta V and zeta potential data shows that adsorption of Celiptium to phosphatidylglycerol not only lowers the electrical surface potential, psi 0 (in absolute value) but also markedly reduces the polarization potential, delta Vp. These observations suggest that Celiptium destabilizes the electrical properties of cell plasma membranes.