Interaction of Mefloquine Hydrochloride with Cell Membranes Models Studied with Tensiometry and Vibrational Spectroscopy

Abstract

Mefloquine hydrochloride is a drug used in the treatment of malaria, with a probable effect on cell membrane surfaces. However, the mechanism of action when they interact with lipid surfaces is not sufficiently known so far. For this reason, it is important the understanding at the molecular level of drug-membrane interactions, and using models for biointerfaces membranes is a suitable strategy for this purpose. In this study, we employed Langmuir monolayers of lipids as biointerface models, with the drug incorporated in monolayers of zwitterionic lipids, namely DPPC (dipalmitoyl phosphatidyl choline), negative lipids, namely DPPS (dipalmitoyl phosphatidyl serine), and cholesterol. Combining data on Surface Pressure-Area Isotherms with Polarization Modulation Infrared Reflection-Absorption Spectroscopy (PM-IRRAS), the effect of the mefloquine hydrochloride on lipid monolayers was compared by taking into account the chemical and molecular structure of the lipids and the drug. The adsorption of the drug at the monolayers decreases the order of the lipid film, replaces water molecules from the interface, in mechanisms that involve both polar head groups and alkyl tails from the lipids. A model is then proposed in which mefloquine hydrochloride interacts with lipids at the air-water in such a way that the interactions are maximized owing to geometrical adaptations on behalf of the contact between lipid polar heads and polar drug groups.