Adsorption behaviour of local anaesthetics in synthetic lipid membranes coated on a quartz-crystal microbalance and correlations with their anaesthetic potencies

Abstract

The partition coefficients in a lipid matrix of seven local anaesthetics in clinical use were obtained using quartz-crystal microbalance (QCM) coated with a synthetic lipid multibilayer film; the resonance frequency of the QCM changes linearly with the amount adsorbed by the lipid matrix. A good correlation was observed between the partition coefficients so determined and the intrinsic local anaesthetic potencies of the same compounds obtained from biological experiments: anaesthetics that induce strong local anaesthesia showed greatest partition into the lipid matrix. The partition coefficients depended on the phase transition of the lipid matrix on the QCM and the ambient pH in the aqueous phase. The uncharged form of amino-type local anaesthetics is strongly adsorbed by the lipid membrane and penetrates deeply into the lipid matrix, especially in the fluid liquid-crystalline state above the phase-transition temperature (T_c), compared with the cationic anaesthetic species present in acidic aqueous solutions.