Facial Amphiphilicity-Induced Polymer Nanostructures for Antimicrobial Applications

Abstract

New antimicrobial agents are needed to address ever-increasing antimicrobial resistance and a growing epidemic of infections caused by multidrug resistant pathogens. We design nanostructured antimicrobial copolymers containing multicyclic natural products that bear facial amphiphilicity. Bile acid based macromolecular architectures of these nanostructures can interact preferentially with bacterial membranes. Incorporation of polyethylene glycol into the copolymers not only improved the colloidal stability of nanostructures but also increased the biocompatibility. This study investigated the effects of facial amphiphilicity, polymer architectures, and self-assembled nanostructures on antimicrobial activity. Advanced nanostructures such as spheres, vesicles, and rod-shaped aggregates are formed in water from the facial amphiphilic cationic copolymers via supramolecular interactions. These aggregates were particularly interactive toward Gram-positive and Gram-negative bacterial cell membranes and showed low hemolysis against mammalian cells.

Hemolytic and Antimicrobial Activities of a Series of Cationic Amphiphilic Copolymers Comprised of Same Centered Comonomers with Thiazole Moieties and Polyethylene Glycol Derivatives

“…Therefore, these differences in cell walls play a crucial role in the susceptibility of microbes to cationic polymers. Typically, Gram-negative and fungi are more difficult to eliminate than Gram-positive [9], but contrary behaviors have been proven for some cationic polymeric systems [10] and broad-spectrum antimicrobial polymers have also been developed [11][12][13]. Some studies concluded that cationic charge influences more the interaction with the bacterial membrane of Gram-positive bacteria in comparison with Gram-negative bacteria, while the hydrophobicity and amphiphilic balance of the polymers affects more the efficacy against Gram-negative bacteria [6,14].…”

Physiology and Physical Chemistry of Bile Acids

“…Moreover, a class of BA-based antibiotics termed Ceragenins have been prepared by covalently attaching amines to BAs, inspired by the molecular structure of squalamine, a naturally occurring aminosterol with potent antimicrobial activity, isolated from shark liver [101][102][103]. Similar molecules have been linked as pendants to polymers able to locally cluster the facial amphiphilicity of these cationic steroid antibiotics, thereby enhancing interactions with bacterial membranes [104][105][106] (Figure 3g-i). To date, BAs are actually used both as precursor and co-agent in drug formulation.…”

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

“…Pioneer studies suggest that amphiphilicity is one of the most important factors determining antimicrobial activity, cytotoxicity, and selectivity of SMAMPs 15 , 88 . Similar to AMPs, their amphiphilic nature enables SMAMPs to electrostatically interact with the bacterial membrane, whereas their hydrophobic moiety could intensify the interaction of peptidomimetics into the hydrophobic core of the bacterial lipid bilayer 41 , 89 . However, because less negatively charged lipids are found in the outer leaflet of the mammalian membrane than in the bacterial membrane, an excessive proportion of hydrophobic segments in SMAMPs will result in undesired hemolysis and deterioration of selectivity owing to a significant decrease in the charging effect 88 .…”