A polytherapy based approach to combat antimicrobial resistance using cubosomes

Abstract

A depleted antimicrobial drug pipeline combined with an increasing prevalence of Gram-negative ‘superbugs’ has increased interest in nano therapies to treat antibiotic resistance. As cubosomes and polymyxins disrupt the outer membrane of Gram-negative bacteria via different mechanisms, we herein examine the antimicrobial activity of polymyxin-loaded cubosomes and explore an alternative strategy via the polytherapy treatment of pathogens with cubosomes in combination with polymyxin. The polytherapy treatment substantially increases antimicrobial activity compared to polymyxin B-loaded cubosomes or polymyxin and cubosomes alone. Confocal microscopy and neutron reflectometry suggest the superior polytherapy activity is achieved via a two-step process. Firstly, electrostatic interactions between polymyxin and lipid A initially destabilize the outer membrane. Subsequently, an influx of cubosomes results in further membrane disruption via a lipid exchange process. These findings demonstrate that nanoparticle-based polytherapy treatments may potentially serve as improved alternatives to the conventional use of drug-loaded lipid nanoparticles for the treatment of “superbugs”.

Gallium Protoporphyrin Liquid Crystalline Lipid Nanoparticles: A Third-Generation Photosensitizer against Pseudomonas aeruginosa Biofilms

“…Secondly, the attachment of LCNP to Pseudomonas biofilms forming a coating patch [ 34 ] that helps overcome 1 O 2 limitations of short lifetime and short diffusion length (3.5 µs and ~100 nm) [ 47 ]. Thirdly, despite their negative charge, LCNP can alter P. aeruginosa cell wall permeability via quick fusion with bacterial outer membranes, such as cationic entities [ 48 ]. All these mechanisms combined qualifies GaPP-LCNP to be a promising photosensitizer against resistant localized infections.…”

Influence of cationic groups on the antibacterial behavior of cationic nano-sized hyperbranched polymers to enhance bacteria-infected wound healing

“…The results further indicated that Q 12 -CNHBP was less likely to induce bacteria to develop resistance compared to conventional antibiotics that target specific intracellular materials. 55–58…”

Coassembled Nitric Oxide-Releasing Nanoparticles with Potent Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains

“…The use of nanoparticle-based antimicrobial systems in combination with conventional antibiotics to improve the bactericidal efficacy is proved to be a promising strategy; 34 therefore, we are motivated to understand whether these six compounds work in synergy with the last-line antibiotic, daptomycin, against MRSA strains or not. Synergy studies were performed by using these six compounds in combination with daptomycin against three MRSA strains and one SA strain (Table S4).…”