Effect of Star Topology Versus Linear Polymers on Antifungal Activity and Mammalian Cell Toxicity

• Published in: Macromolecular bioscience 2024-05, Vol.24 (5), p.e2300452-n/a
• Main Authors: Schaefer, Sebastian, Melodia, Daniele, Corrigan, Nathaniel, Lenardon, Megan Denise, Boyer, Cyrille
• Format: Article
• Language: English
• Subjects: Addition polymerization; Amphotericin B; Amphotericin B - chemistry; Amphotericin B - pharmacology; Animals; Antifungal activity; antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial peptides; antimicrobial polymers; Biocompatibility; Candida albicans - drug effects; Candida albicans - growth & development; Cell Line; Clinical isolates; controlled/living radical polymerisation; Drug development; Embryo fibroblasts; Erythrocytes; Erythrocytes - drug effects; Fibroblasts - drug effects; Fungi; Fungicides; Hemolysis - drug effects; Mice; Microbial Sensitivity Tests; Minimum inhibitory concentration; Molecular weight; Peptides; polymer topology; Polymers; Polymers - chemistry; Polymers - pharmacology; Topology; Toxicity
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202300452

The global increase in invasive fungal infections and the emergence of drug‐resistant strains demand the urgent development of novel antifungal drugs. In this context, synthetic polymers with diverse compositions, mimicking natural antimicrobial peptides, have shown promising potential for combating fungal infections. This study investigates how altering polymer end‐groups and topology from linear to branched star‐like structures affects their efficacy against Candida spp., including clinical isolates. Additionally, the polymers’ biocompatibility is accessed with murine embryonic fibroblasts and red blood cells in vitro. Notably, a low‐molecular weight star polymer outperforms both its linear polymeric counterparts and amphotericin B (AmpB) in terms of an improved therapeutic index and reduced haemolytic activity, despite a higher minimum inhibitory concentration against Candida albicans (C. albicans) SC5314 (16–32 µg mL−1 vs 1 µg mL−1 for AmpB). These findings demonstrate the potential of synthetic polymers with diverse topologies as promising candidates for antifungal applications. Synthetic polymers inspired by natural antimicrobial peptides have shown promise for the treatment of fungal infections. The present study compares linear to star‐like topology of amphiphilic, positively charged polymers. A low‐Xn 3‐arm polymer shows favourable activity against Candida spp. and biocompatibility with fibroblasts. Additionally, the tested star‐polymers show an increased compatibility with red blood cells, compared to their linear counterparts.