Phenazine-1-carboxamide functionalized mesoporous silica nanoparticles as antimicrobial coatings on silicone urethral...

Microbial infections due to biofilms on medical implants can be prevented by antimicrobial coatings on biomaterial surfaces. Mesoporous silica nanoparticles (MSNPs) were synthesized via base-catalyzed sol-gel process at room temperature, functionalized with phenazine-1-carboxamide (PCN) and characterized by UV-visible, FT-IR, DLS, XRD spectroscopic techniques, SEM, TEM, TGA and BET analysis. Native MSNPs, PCN and PCN-MSNPs were evaluated for anti-Candida minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), Candida albicans (C. albicans) biofilms and C. albicans-Staphylococcus aureus (S. aureus) polymicrobial biofilm inhibition. PCN-MSNPs were four-fold effective (MIC 3.9 µg mL^-1; 17.47 µM) and MFC (7.8 µg mL^-1; 34.94 µM) as compared to pure PCN (MIC 15.6 µg mL^-1; 69.88 µM) and MFC (31.2 µg mL^-1; 139.76 µM). PCN-MSNPs inhibited in vitro C. albicans MTCC 227-S. aureus MTCC 96 biofilms at very low concentration (10 µg mL^-1; 44.79 µM) as compared to pure PCN (40 µg mL^-1; 179.18 µM). Mechanistic studies revealed that PCN induced intracellular ROS accumulation in C. albicans MTCC 227, S. aureus MTCC 96 and S. aureus MLS-16 MTCC 2940, reduction in total ergosterol content, membrane permeability, disruption of ionic homeostasis followed by Na⁺, K⁺ and Ca²⁺ leakage leading to cell death in C. albicans MTCC 227 as confirmed by confocal laser scanning micrographs. The silicone urethral catheters coated with PCN-MSNPs (500 µg mL^-1; 2.23 mM) exhibited no formation of C. albicans MTCC 227 - S. aureus MTCC 96 and C. albicans MTCC 227 - S. aureus MLS -16 MTCC 2940 biofilms. This is the first report on PCN-MSNPs for use as antimicrobial coatings against microbial adhesion and biofilm formation on silicone urethral catheters.