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

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.