A nanocarrier system that potentiates the effect of miconazole within different interkingdom biofilms

Abstract

Background: Novel and new therapeutic strategies capable of enhancing the efficacy of existing antimicrobials is an attractive proposition to meet the needs of society. Objective: This study aimed to evaluate the potentiating effect of a miconazole (MCZ) nanocarrier system, incorporated with iron oxide nanoparticles (IONPs) and chitosan (CS) (IONPs-CS-MCZ). This was tested on three representative complex interkingdom oral biofilm models (caries, denture and gingivitis). Materials and methods: The planktonic and sessile minimum inhibitory concentrations (MICs) of IONPs-CS-MCZ against different Candida albicans strains were determined, as well as against all represented bacterial species that formed within the three biofilm models. Biofilms were treated for 24 hours with the IONPs-CS nanocarrier system containing MCZ at 64 mg/L, and characterized using a range of bioassays for quantitative and qualitative assessment. Results: MIC results generally showed that IONPs-CS-MCZ was more effective than MCZ alone. IONPs-CS-MCZ also promoted reductions in the number of CFUs, biomass and metabolic activity of the representative biofilms, as well as altering biofilm ultrastructure when compared to untreated biofilms. IONPs-CS-MCZ affected the composition and reduced the CFEs for most of the microorganisms present in the three evaluated biofilms. In particular, the proportion of streptococci in the biofilm composition were reduced in all three models, whilst Fusobacterium spp. percentage reduced in the gingivitis and caries models, respectively. Conclusion: In conclusion, the IONPs-CS-MCZ nanocarrier was efficient against three in vitro models of pathogenic oral biofilms, showing potential to possibly interfere in the synergistic interactions among fungal and bacterial cells within polymicrobial consortia.

Candida albicans as an Essential “Keystone” Component within Polymicrobial Oral Biofilm Models?

“…It should also be noted that only normal qPCR, and not live/dead qPCR, was used to quantify the bacterial and fungal load in the models following treatment. This live/dead methodology has been used with great effect to assess the level of “viability” of oral microorganisms in plaque samples and in vitro biofilm models [ 38 , 44 , 95 ]. Therefore, it could be that no changes were observed in the total bacterial or fungal load in this study, but there may have been reductions in the number of viable cells present in the biofilm (which could corroborate with the metabolic activity changes particularly for CHX treatment for example).…”

Filling the Void: An Optimized Polymicrobial Interkingdom Biofilm Model for Assessing Novel Antimicrobial Agents in Endodontic Infection

“…Another study also showed that solubilized chitosan was effective in reducing the viability of three single-species biofilms containing Streptococcus mutans , Actinomyces naeslundii , and Enterococcus faecalis [ 54 ]. Our group has recently shown chitosan within a nanocarrier system to be effective against interkingdom biofilms representing caries (five species), gingivitis (seven species), and denture stomatitis (11 species) [ 55 ]. Here, we show with our optimized endodontic model that chitosan is particularly effective in inhibiting regrowth of a mixed-species biofilm model following physical debridement.…”

Microbial Interkingdom Biofilms and the Quest for Novel Therapeutic Strategies

“…Thus, CDX-loaded nanocarriers may promote a higher antibiofilm effect of the drug, while lowering its toxicity toward human cells [ 142 ]. Magnetic NPs coated with chitosan were also used to load miconazole, a drug with both antibacterial and antifungal properties [ 143 , 158 ]. This formulation was further tested on three representative interkingdom oral biofilms (caries, denture, and gingivitis) [ 143 ].…”

“…Magnetic NPs coated with chitosan were also used to load miconazole, a drug with both antibacterial and antifungal properties [ 143 , 158 ]. This formulation was further tested on three representative interkingdom oral biofilms (caries, denture, and gingivitis) [ 143 ]. In all three models, nanocarriers containing miconazole significantly reduced the number of viable cells.…”

“…In addition, fewer hyphae were observed in the presence of the designed NPs, which suggests an inhibition of C. albicans hyphal form during treatment. Consequently, the support provided by hyphae to bacteria is partially lost, explaining the lower numbers of bacterial cells [ 143 ].…”