Interaction of electrically charged drug molecules with phospholipid membranes.

Model membranes (egg-yolk PC liposomes) were exposed to the cationic form of amphiphilic drugs. Microelectrophoresis was used to measure the change of the electrokinetic potential as a function of the drug concentration. By use of the Gouy-Chapman theory the surface potential and surface charge density were calculated. A theoretical model postulating a simple partition equilibrium of the charged drug molecules between the membrane and the aqueous phase in the vicinity of the membrane failed to describe the experimental results. Modification of the partition law by introducing a mechanism of saturation at high drug concentrations, however, resulted in concordance of model and experiment. Some parameters of the model can be used as a means of evaluating the efficiency of neuroactive drugs.