Interaction kinetics of salmeterol with egg phosphatidylcholine liposomes by surface plasmon resonance

Surface plasmon resonance (SPR) Biacore™ and equilibrium dialysis were applied to investigate the membrane affinities of salmeterol and propranolol and the kinetic interactions of salmeterol with egg phosphatidylcholine liposomes. The two methods revealed similar affinity values; however, they were dependent on the investigated drug concentrations. The kinetic experiments with salmeterol were optimized to obtain pseudo-first-order kinetics that were independent of the drug concentration. The adsorption and desorption phases followed biexponential functions up to pH 8.8 and mono or biexponential functions at higher pH values (i.e., between the two pK_a values). The apparent rate constants of the faster phases of the biexponential functions were beyond the time resolution of the instrument in most measurements. The apparent rate constants of the slower phases ranged from 0.01 to 0.03 s⁻¹ and were pH independent between pH 5.0 and pH 8.0. The rates of the monoexponential kinetics were between 0.08 and 0.12 s⁻¹. We conclude that the biexponential kinetics at physiological pH reflect the partitioning into the outer lipid leaflet and “flip-flop,” respectively, of the cationic species.