Interaction of the cationic form of amphiphilic drugs with phosphatidylcholine model membranes. Competition with lanthanide ions.

Model membranes (liposomes) of egg yolk phosphatidylcholine were exposed to the charged (cationic) form of amphiphilic drugs (procaine, tetracaine, metroprolol, alprenolol and propranolol). Drug analysis by ultraviolet light absorption of the bulk solution after centrifugation separation was used to determine the amount of drug bound to the membranes. Microelectrophoresis was employed to measure the change in the zeta-potential after drug adsorption. Binding constants were derived by simulating the experimental curves with a theoretical model which considers the electrostatic effects (Gouy-Chapman theory). Analogous experiments were carried out for the adsorption of Eu3+. Metal analysis was made by three different methods. Good agreement between the centrifugation and electrophoresis experiments was obtained for reasonable positions of the plane of shear relative to the positional plane of the bound ions. Displacement of Eu3+ from vesicles upon addition of drug cations was followed by 31P-NMR. The competition experiments were numerically simulated. The Eu3+ binding was assumed to obey a mass action type equilibrium, whereas the drug binding was described by a Henry's law partition. The binding constants for the drugs in the competition experiments followed the same order as in the absence of Eu3+. However, the numerical values had to be reduced. The effect of anions was studied.