Effect of tetracaine on DMPC and DMPC+cholesterol biomembrane models: liposomes and monolayers.

Different types of lipid bilayers/monolayers have been used to simulate the cellular membranes in the investigation of the interactions between drugs and cells. However, to our knowledge, very few studies focused on the influence of the chosen membrane model upon the obtained results. The main objective of this work is to understand how do the nature and immobilization state of the biomembrane models influence the action of the local anaesthetic tetracaine (TTC) upon the lipid membranes. The interaction of TTC with different biomembrane models of dimyristoylphosphatidylcholine (DMPC) with and without cholesterol (CHOL) was investigated through several techniques. A quartz crystal microbalance with dissipation (QCM-D) was used to study the effect on immobilized liposomes, while phosphorus nuclear magnetic resonance ((31)P-NMR) and differential scanning calorimetry (DSC) were applied to liposomes in suspension. The effect of TTC on Langmuir monolayers of lipids was also investigated through surface pressure-area measurements at the air-water interface. The general conclusion was that TTC has a fluidizing effect on the lipid membranes and, above certain concentrations, induces membrane swelling or even solubilization. However, different models led to variable responses to the TTC action. The intensity of the disordering effect caused by TTC increased in the following order: supported liposomes<liposomes in solution<Langmuir monolayers. This means that extrapolation of the results obtained in in vitro studies of the lipid/anaesthetic interactions to in vivo conditions should be done carefully.