Towards the development of supramolecular self-associating amphiphiles as antibiofilm agents against <i>Pseudomonas aeruginosa</i> and <i>Candida albicans</i> biofilms

The rise of antimicrobial resistant (AMR) infection represents a growing threat to the global population and to economic health. The majority of antimicrobial innovations are developed against planktonic microorganisms, however those same microorganisms contained within a biofilm can become over 1000 times more resistant to antimicrobial (including antibiotic) agents. Supramolecular self-associating amphiphiles (SSAs) are a class of amphiphilic salts and related compounds that have shown the potential for development into antibiofilm agents. Within the scope of this work we present five structurally diverse SSAs. We characterise the self-associative properties of these SSAs in the solid state and in solution, before analysing the interactions of these agents with model synthetic membranes and determining their antibiofilm activity against WHO high/critical priority pathogens, <i>Pseudomonas aeruginosa</i> and <i>Candida albicans</i>. We also combine SSAs as 1:1 co-formulations and confirm the combination of SSA to inform both SSA phospholipid membrane interaction events and biological activity. Finally, we undertake a series of <i>in vitro</i> and <i>in vivo</i> DMPK experiments to verify the drug-like properties for these structurally diverse SSAs.