Benzalkonium Chloride-Loaded p(HEMA) vs. p(HEMA-co-MA) Hydrogels: Enhancing Antimicrobial and Antibiofilm Efficacy Through Maleic Anhydride Functionalization

Catheter-associated urinary tract infections are often caused by biofilm formation on device surfaces. This paper presents an antimicrobial catheter-coating hydrogel comprising p(HEMA) and carboxyl-functionalized p(HEMA-co-MA), loaded with benzalkonium chloride (BAC) to increase hydrophilicity, pH responsiveness, and antibiofilm activity. Hydrogels were prepared by free-radical polymerization, loaded with BAC via swelling, and their physicochemical properties were characterized. Furthermore, microbiological assessment focused on the detection of MIC/MBC/MFC, disk diffusion, biofilm assays, SEM imaging, and RT-qPCR sequencing were used to determine the impact on biofilm-related gene expression to evaluate antimicrobial activity against major catheter-associated urinary tract infection (CAUTI)-associated pathogens and identify the higher BAC loading p(HEMA) and enhanced hydrophilicity and pH-responsive swelling (p(HEMA-co-MA)). The two hydrogels exhibited a wide range of antimicrobial activity and provided lasting inhibition for up to 8 days. It is worth noting that the MA-functionalized hydrogel exhibited a high intrinsic antifouling property, and biofilm development was reduced by more than 85% in BAC-loaded formulations. SEM and gene-expression studies showed reduced microbial adhesion and substantial repression of virulence and biofilm-associated genes. In summary, BAC-loaded p(HEMA) and p(HEMA-co-MA) coatings exhibit strong antimicrobial and antiadhesive properties, and the incorporation of MA results in more effective biofilm suppression, which supports their future use as advanced catheter coatings to prevent the development of device-related infections.