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

Abstract

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 Ca 2+ 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.

Nanoparticles as Potential Novel Therapies for Urinary Tract Infections

“…The authors also did a polymicrobial inhibition assay using agar well diffusion method against a mixture of C. albicans and S. aureus. The assay revealed that both PCN and PCN-MSNPs inhibited the growth of mixed pathogens, but PCN-MSNPs showed a greater inhibitory effect, (Kanugala et al, 2019).…”

“…Nowadays, inorganic NPs are widely considered as catheters coating, among which AgNPs are already being used to prevent catheter bacterial colonization, while other inorganic materials are currently under investigation. All reported inorganic compounds-based NPs as well as organic NPs, show a tendency to be include in urinary tract devices to prevent biofilm formation and reduce CAUTIs (Meenakumari et al, 2000;Ulett et al, 2007;Syed et al, 2009;Syed et al, 2010;Evliyaoglu et al, 2011;Agarwala et al, 2014;Prabha et al, 2014;Ahmed et al, 2016;Shafreen et al, 2017;Shalom et al, 2017;Bhargava et al, 2018;Hosseini et al, 2018;Rajivgandhi et al, 2018;Divya et al, 2019;Iribarnegaray et al, 2019;Hosseini et al, 2019;Kanugala et al, 2019). Furthermore, some investigations have exposed that their synthetized NPs could have the potential to be used either as a catheter coating or as a systemic administration drug.…”

Silica Nanoparticles—A Versatile Tool for the Treatment of Bacterial Infections

“…Incidentally, SiNPs have proven to be indispensable against biofilms with effective inhibitory action on wearable medical implants. Kanugala and colleagues studied the anti-biofilm potential of phenazine-1-carboxamide (PCN)-loaded MSN, coated on silicone urethral catheters (Kanugala et al, 2019 ). The antimicrobial activity of native MSNPs, PCN, and PCN-MSNPs was evaluated against planktonic C. albicans, C. albicans biofilm, and C. albicans - S. aureus polymicrobial biofilm.…”

Microbial Interkingdom Biofilms and the Quest for Novel Therapeutic Strategies

“…The NPs showed a controlled release of PCN over a 40-h period, which contributed to an inhibition higher than 88% of C. albicans-S. aureus biofilms. In fact, PCN-loaded NPs were able to inhibit mixed biofilms at a very low concentration compared to unloaded PCN [145]. In a distinct approach to inhibit formation of C. albicans-S. aureus biofilms in catheters, silicone elastomers were functionalized with silver NPs.…”

“…aureus biofilms. In fact, PCN-loaded NPs were able to inhibit mixed biofilms at a very low concentration compared to unloaded PCN [ 145 ]. In a distinct approach to inhibit formation of C. albicans–S.…”