Probing the interaction of liposomal delivery systems with model Gram-negative bacterial cell envelopes

Antimicrobial resistance (AMR) is a major threat to global public health, particularly with respect to Gram-negative bacteria, for which the resistance is largely a result of their complex double-membrane envelope structure. Liposomes can effectively deliver anti-infectives across the Gram-negative cell envelope, however, the mechanism of liposome-cell envelope membrane interactions is not fully understood. As part of a larger study aiming to characterise the ability of a selection of liposomal formulations to interact with Gram-negative bacteria possessing different cell envelope structures, we propose to perform neutron reflectometry with isotopic contrast variation to investigate the adhesion/fusion or exchange of lipids during the interaction of liposomes with models of the Gram-negative outer membrane (OM) outer leaflet at air/water interface. The results of this work will be invaluable in understanding the interaction of liposomal membranes with the OM of Gram-negative bacteria, and in the improved design of liposomes for the delivery of anti-infective agents.