Electrochemical characterization of a mixed lipid monolayer supported on Au(111) electrodes with implications for doxorubicin delivery

Abstract

The cationic lipid didodecyldimethylammonium bromide (DDAB) is one of the agent that is included in formulations for liposomes with anchored gold nanoparticles as drugs carriers because its positive charge facilitates the anchoring of the negatively charged stabilized gold nanoparticles to the lipid components of the liposomes. In this paper a thermodynamic analysis of Langmuir isotherms was performed, as a first step in the preparation of liposomes including DDAB, the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and cholesterol(Ch),to decide about the most stable combination. Monolayers of DMPC:Ch:DDAB with the most energetically favourable composition, were transferred to Au(111) electrodes by the Langmuir-Schaefer technique in the electrochemical cell and characterized by impedance spectroscopy. The results were compared with those obtained with electrodes coated with DMPC:Ch films that did not contain DDAB. In both cases the frequency dispersion of impedance data indicates high homogeneity of the films in a wide potential range around the capacitance minimum.The inclusion of the anticancer drug doxorubicin (DOX) into the mixed lipid monolayers and its electrochemical reduction at pH 4.5 were studied by voltammetry and by impedance spectroscopy. At potentials out of the faradaic region the inclusion of DOX does not affect significantly the frequency dispersion of the impedance but decreases the capacitance. However, at negative potentials the analysis of the high frequency dispersion of the impedance and the influence of the scan rate on the voltammograms indicate a reduction process with contribution of adsorption and diffusion of DOX.Diffusion was avoided by transferring the electrodes coated in the Langmuir trough to the electrochemical cells that do not contain the drug. Under these conditions the reduction of the adsorbed DOX was found to obey the model of a surface confined electrode and the charge transfer resistance, Ra, and adsorption capacitance, Ca, were obtained at potentials of the faradaic region. The combination of both parameters provides the rate constant for the reduction in a wide potential range that allows us to propose a sequential mechanism with two determining steps.