Novel β-lactam-Octenidine nanoGUMBOS: A promising platform to address Bacteria linked to chronic wound infections.

Antimicrobial resistance is a global health challenge, particularly in chronic wounds (CW), where bacterial colonization and biofilm formation impair healing and promote persistent infections. The limited efficacy of conventional antibiotics against multidrug-resistant pathogens highlights the need for innovative antimicrobial strategies. This study aimed to develop and evaluate β-lactam-octenidine nanoGUMBOS as multifunctional antimicrobial nanomaterials for CW management. Three nanoGUMBOS, [OCT][Cftx], [OCT][Cflt], and [OCT][Cfpz], were synthesized through a simple additive-free reprecipitation method. Their physicochemical properties were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytocompatibility was assessed in fibroblasts (L929) and keratinocytes (HaCaT) cell lines, while antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. DLS and TEM analyses confirmed the formation of homogeneous spherical nanoparticles with diameters of approximately 100 nm and low polydispersity (PDI < 0.2). All compounds were non-cytotoxic up to 9 μM and exhibited higher cell viability than their precursor salts. [OCT][Cftx] and [OCT][Cflt] showed the strongest antibacterial activity, with MIC values as low as 4.5 μM, outperforming both bulk GUMBOS and individual precursors. This study introduces a new class of multifunctional antimicrobial nanoGUMBOS, demonstrates that nanoscale assembly enhances the antimicrobial performance of β-lactam-octenidine GUMBOS while maintaining favorable cytocompatibility. To the best of our knowledge, this is the first report of β-lactam-octenidine nanoGUMBOS, obtained through a simple, automatic and additive-free synthesis approach, highlighting their potential as a promising platform for the treatment of CW, compared with both bulk GUMBOS and precursor compounds.