Interactions of lipid nanocarriers with a bacterial model membrane

Lipid nanocarrier (NC)-mediated delivery of antibiotics (including liposomes, cubosomes and hexosomes) is a promising strategy in dealing with the global issue of antimicrobial resistance and has been shown to improve the efficacy of currently available antibiotics. However, our understanding of the effect of lipid nanostructure on interactions of NCs with bacteria is lacking. Herein, we investigate the interactions of four different lipid NCs (including both cubosomes and hexosomes) with a simple bacterial supported lipid bilayer (SLB) mimicking the lipid bilayer of Escherichia coli (E. coli) using a combination of total internal reflection microscopy (TIRF-M), quartz crystal microbalance with dissipation (QCM-D) and synchrotron radiation small angle X-ray scattering (SR-SAXS). Addition of the fusogenic lipid di-oleoyl phosphatidylethanolamine (DOPE) increased interactions with the SLB, while addition of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) significantly increased interactions. The QCM-D data and SR-SAXS data indicate that mixing of the particles with E. coli mimicking model layers results in significant disruption to the cubosome structure, while hexosomes remain essentially structurally intact. We propose that the interaction mechanism with bacterial membranes differs among lipid NCs; while cubosomes primarily fuse with the lipid bilayer resulting in a loss of internal nanostructure, hexosomes interact with bacterial membranes via a different mechanism which allows them to retain structural integrity.