Interactions of doxorubicin with organized interfacial assemblies. 1. Electrochemical characterization

Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary target of its action being nuclear DNA. Despite the large body of knowledge on this family of compounds, the mechanism of doxorubicin penetration through the cellular or nuclear membrane remains understood to a limited extent. The plasma membrane acts as a barrier to the permeation of polar molecules, and this effect is mainly due to the hydrophobicity of membrane interior. The partitioning of DOX molecules into the lipid bilayer must thus be the basis for its passive transport across the biological membrane and therefore a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and Langmuir/Langmuir-Blodgett monomolecular films of octadecylamine (C18NH2), dihexadecylphosphate (DHP) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and DMPC bilayer films (Langmuir-Schaeffer) on a polycrystalline gold surface using ellipsometry, cyclic voltammetry, electrochemical impedance spectroscopy, and quartz crystal microbalance measurements. For all biomimetic films there is a substantial interaction between doxorubicin and the interface, and the extent of this interaction depends on the hydrophobic/hydrophilic properties of the film formed and its organization.