Abstract Statement of problem Incorporating antifungals into interim denture resilient liners has been proposed to prolong their clinical longevity and to treat denture stomatitis. However, ...information is lacking on the effect of this addition on water sorption and solubility. Purpose The purpose of this in vitro study was to evaluate the addition of minimum inhibitory concentrations (MICs) of antifungals for Candida albicans biofilm on the water sorption (WS) and solubility of interim denture resilient liners. Material and methods Disk-shaped specimens (n=10; 50×0.5 mm) of tissue conditioner (Softone) and resilient liner (Trusoft) were created either without (control) or with the incorporation of 1 of the 3 following drugs at MICs (g of drug per g of resilient material powder): nystatin (Ny, 0.032g/g), chlorhexidine diacetate (Chx, 0.064g/g), and ketoconazole (Ke, 0.128g/g). Specimens were dried; immersed in water for 24 hours and 7 or 14 days; weighed, dried, and weighed again. Data (μg/mm3 ) were analyzed by 3-way ANOVA followed by the Tukey-Kramer honest significant differences test (α=.05). Results At the 14-day interval, only the addition of Chx (483.0 ±61.0 μg/mm3 ) increased the WS of the tissue conditioner compared with the control group (244.0 ±42.0 μg/mm3 ; P< .001). For all periods, the solubility of both materials increased with the addition of Chx (27.7 ±6.1 μg/mm3 ) and Ke (30.9 ±5.3 μg/mm3 ) compared with the control group (22.5 ±6.0 μg/mm3 ; P< .001). Conclusions After 14 days, the addition of Ny and Ke at MICs in both Softone and Trusoft and addition of Chx in Trusoft did not affect WS. The solubility of the 2 interim materials was not altered by the addition of Ny for up to 14 days.
Antifungal agents incorporated into temporary denture resilient liners as drug carriers and delivery have been suggested as an alternative treatment for denture stomatitis. However, to test the in ...vivo biocompatibility of this protocol, standardization of an intraoral device for optimal drug delivery is required.
Standardized criteria were produced to adjust an acrylic intraoral device (IOD) for rats feasible for denture stomatitis treatment by sustained drug-delivery based on minimal inhibitory drug concentrations (MICs) of antifungals for Candida albicans biofilm.
Adjustments methodological involved diet, impression technique, type of retention device to the palate and histopathological analysis. 115 Wistar rats were tested without IOD, with devices without relining or relined with temporary resilient material (Trusoft) modified or not by drugs at MICs (nystatin-0.032g/mL; chlorhexidine diacetate-0.064g/mL; ketoconazole-0.128g/mL). The animals were sacrificed after 7 or 14 days from the IOD installation.
Paste diet enabled the best animal survival conditions. The IODs that most satisfactorily remained in position were those designed only to the posterior palatal mucosa and cement-retained in molars, being all obtained from impressions highly detained and individual. In both periods, Trusoft without/with drugs showed good performance. Only histological samples from hard/soft tissues were considered appropriate for region of interest-RI determination (n=12), which corresponded to the area restricted to the first molars between the palatal neurovascular bundles. Final samples of all groups allowed a standardized descriptive histopathological analysis in both periods.
The methodological standardization of this rat model resulted in IODs for optimal antifungal delivery for denture stomatitis treatment.
This randomized clinical trial evaluated the effectiveness of an interim denture resilient liner (Trusoft) modified with minimum inhibitory concentrations (MICs) of antimicrobial agents for Candida ...albicans biofilm in the denture stomatitis (DS) treatment.
Forty participants with DS and maxillary complete denture (MCD) wearers were randomly assigned to one of the treatments for 14 days (n=10): nystatin oral suspension (Control-100,000IU/mL; 4 × /day), MCD relined with Trusoft either without (Tru) or with nystatin (Ny) or chlorhexidine diacetate (Chx) at MICs. Cytological smears and mycological quantitative cultures were taken from the palate and denture before treatment (baseline), at the end of treatment (day 14), and at follow-up (days 30, 45, and 60). Photographs of the palate were made at each visit. Data were analyzed by the Cochran and χ2 tests, ANOVA and the Tukey test or the Friedman and Kruskal-Wallis tests (α=0.05).
Palatal smears of the Ny and Chx groups exhibited no mycelial Candida (0%) on day 14, and, at the 60-day follow-up, it was observed for only 1 participant from Chx group. MCD smears showed reduction in mycelial forms for all groups on day 14 (P<0.05), but this difference was maintained at follow-up only for the relined dentures (P<0.05). Unlike Tru and the control groups, Ny and Chx groups evidenced a significant reduction in CFU/mL values and DS severity throughout the trial (P<0.05).
The addition of nystatin and chlorhexidine at MICs to an interim resilient liner is a promising treatment for DS, with better results than those for conventional therapy with nystatin suspension, including the follow-ups.
Compared with conventional topical antifungal therapy, modifying a denture reline material with antimicrobials provided a therapeutic option for denture stomatitis. This non-invasive, straightforward therapeutic approach can be easily adopted by dentists and has the advantage of not requiring patient compliance while maintaining therapeutic concentrations on the denture base.
Two soft denture lining materials (SC-Soft Confort and TS-Trusoft) were investigated with and without the addition of 1.0% of chlorhexidine diacetate (1.0% CHX). To assess peel bond strength, ...specimens (75×10×6 mm) were submitted to a peel test at 10 mm/min immediately and after 24 h. To evaluate Candida albicans growth inhibition, disc of specimens (10×3 mm) were immersed in a solution with 3×106 CFU/mL of C. albicans, and spectral measurements were made following immersion in MTT solution for 2, 4, and 6 days. The agar diffusion test was performed by investigating the diameters of inhibition zones around the disc of specimens (10×3 mm)after 48 h. Data were submitted to statistical analysis (α=0.05) and the failure modes were visually classified. The incorporation of 1.0% CHX significantly decreased the peel bond strength for TS (p=0.001) and SC (p=0.005) for immediate test and for TS after 24 h (p=0.010), but not for SC. C. albicans growth was decreased for both materials over time (p<0.05). SC presented inhibition zones approximately 2.0 times larger than TS. The incorporation of 1.0% CHX inhibited fungal growth without impairment to the peel bond strength for SC after 24 h.
The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could ...optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with β‐cyclodextrin (βCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl‐thiazolyl‐tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one‐way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the βCD‐complexed antifungals were less toxic against A. salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5 mg/L; Nys:βCD 4 mg/L; Chx 4 mg/L; and Chx:βCD 8 mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with βCD might be a biocompatible option for the treatment of Candida‐related infections.
Our study aimed to evaluate the in vitro toxicity of nystatin and chlorhexidine complexed with β‐cyclodextrin (βCD) against Artemia salina, to determine their minimum inhibitory concentrations against Candida albicans, and to assess their cytotoxicity on murine fibroblasts at these concentrations. The complexed antifungals were less toxic to A. salina than their raw forms. βCD‐complexed drugs also showed excellent antifungal activity against C. albicans and did not promote cellular damage.
No information is available on roughness and stainability of acrylic resins polymerized by experimental microwave cycles after immersion in stainable liquids and simulated brushing.
The purpose of ...this in vitro study was to evaluate the effect of stainable drinks and brushing on roughness and stainability of acrylic resins (Vipi Cril CA and Vipi Wave MA) polymerized with different cycles.
CA and MA specimens (n=5; diameter, 20 mm; thickness, 3 mm) were made using 4 methods recommended by the manufacturer (water bath polymerization and microwave polymerization cycles) and experimental at 550 W or 650 W for 3 or 5 minutes (M550/3 and M650/5), respectively. After storage in distilled water at 37°C for 48 hours (T0), the specimens were stored in water, coffee, or red wine (37°C) for 36 days with simulated brushing (54 000 cycles, T1). Roughness (Ra) and stainability (ΔE/National Bureau of Standards) were measured at T0 and T1. Roughness and stainability data were analyzed by 3-way repeated measures and 2-way ANOVA, respectively, followed by the Bonferroni test (α=.05).
After storing in coffee and brushing, CA showed the highest (M550/3=2.33 ±0.72 μm) and the lowest roughness (water bath polymerization=1.22 ±0.58 μm), whereas roughness of MA specimens processed by M650/5 increased (1.57 ±0.59 μm). Storing in wine and brushing increased roughness (1.75 ±0.32 μm) in the M550/3 group. No staining was observed on MA after brushing regardless of the polymerization cycle. All values were acceptable (ΔE≤3.3), except for MA (microwave polymerization), which showed National Bureau of Standards=4.49 (appreciable change) after storing in wine and brushing.
A slight increase in material roughness was observed after staining and brushing. Only MA polymerized following manufacturer cycles showed relevant stainability after immersion in wine and brushing.
Purpose
While the incorporation of antimicrobial agents into soft denture liners has been suggested as a reliable alternative treatment for denture stomatitis, it may affect the liner's properties. ...The effect of addition of antimicrobial agents for the treatment of denture stomatitis on the surface roughness and Shore A hardness of soft lining materials was evaluated.
Materials and Methods
The test groups comprised specimens (36 × 7 × 6 mm3) of soft materials (Softone and Trusoft) without (control) or with incorporation of drugs (nystatin, miconazole, ketoconazole, chlorhexidine diacetate, and itraconazole). Hardness (Shore A) and roughness (Ra) were evaluated after immersion of specimens (n = 10) in distilled water at 37°C for 24 hours, 7 and 14 days. Data were analyzed by 3‐way ANOVA/Tukey's test (α = 0.05).
Results
After 14 days, an increase (p < 0.05) was observed in the hardness of soft materials with time for the modified specimens, except for itraconazole. Addition of drugs increased the Softone roughness only for the addition of miconazole and chlorhexidine (p < 0.05), and did not increase the roughness of Trusoft with time. Only chlorhexidine and itraconazole altered the roughness compared to the control for each material (p < 0.05).
Conclusions
The smallest changes of hardness and roughness with time in the modified groups compared to controls were observed for itraconazole groups for both materials.
The effect of the addition of nystatin, miconazole, ketoconazole, chlorhexidine, and itraconazole into the soft lining materials Softone and Trusoft on their peel bond strength to a denture base ...acrylic resin was evaluated. Specimens of soft lining materials (n=7) were made without (control) or with the incorporation of antifungals at their minimum inhibitory concentrations to the biofilm of C. albicans and bonded to the acrylic resin. Peel testing was performed after immersion in distilled water at 37ºC for 24 h, 7 and 14 days. Data (MPa) were analyzed by 3-way ANOVA/Tukey-Kramer test (α=0.05) and the failure modes were classified. The addition of nystatin and ketoconazole did not affect the peel bond strength for up to 14 days. Most failures were predominantly cohesive within soft lining materials. With the exception of itraconazole, incorporating the antifungals into the soft lining materials did not result in values below those recommended for peel bond strength after 7 and 14 days of analysis.
Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug, according to the Biopharmaceutical Classification ...System, that possesses limited bioavailability and is used for local activity.
This study developed and characterized nystatin:β-cyclodextrin (Nys:βCD) inclusion complexes and evaluated their activity against
spp.
Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of
and
was assessed using the broth microdilution method. The applicability of Nys:βCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment.
Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:βCD complex presents antifungal activity against all evaluated
strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys.
This work represents a significant contribution to treating a wide variety of diseases caused by the
species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.