Silver chitosan nanocomposites as a potential treatment for superficial candidiasis.

Silver compounds are widely known for their antimicrobial activity, but can exert toxic effects to the host. Among the strategies to reduce its toxicity, incorporation into biopolymers has shown promising results. We investigated the green syntheses of silver nanoparticles (AgNPs) and their functionalization in a chitosan matrix (AgNPs@Chi) as a potential treatment against Candida spp. Inhibitory concentrations ranging between 0.06 and  1 µg/ml were observed against distinct Candida species. Nanocomposite-treated cells displayed cytoplasmic degeneration and a cell membrane and wall disruption. Silver nanocomposites in combination with fluconazole and amphotericin B showed an additive effect when analyzed by the Bliss method. The low cytotoxicity displayed in mammalian cells and in the Galleria mellonella larvae suggested their potential use in vivo. When tested as a topical treatment against murine cutaneous candidiasis, silver nanocomposites reduced the skin fungal burden in a dose-response behavior and favored tissue repair. In addition, the anti-biofilm effect of AgNPs@Chi in human nail model was demonstrated, suggesting that the polymeric formulation of AgNPs does not affect antifungal activity even against sessile cells. Our results suggest that AgNPs@Chi seems to be a less toxic and effective topical treatment for superficial candidiasis. LAY SUMMARY: This study demonstrated the efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Candida. AgNPs incorporated in chitosan displayed a reduced toxicity. Tests in infected mice showed the effectiveness of the treatment. AgNPs-chitosan could be an alternative to combat candidiasis.

A lipase-responsive antifungal nanoplatform for synergistic photodynamic/photothermal/pharmaco-therapy of azole-resistant Candida albicans infections.

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.

Antifungal activity of essential oils extract from Origanum floribundum Munby, Rosmarinus officinalis L. and Thymus ciliatus Desf. against Candida albicans isolated from bovine clinical mastitis.

OBJECTIVE: The aim of this study is to limit the antibiotic use in mastitis treatment and to find other alternatives. The antifungal activity of the essential oils from Origanum floribundum Munby., Rosmarinus officinalis L. and Thymus ciliatus Desf. is studied in the present work against a Candida albicans reference strain and ten C. albicans isolated strains from bovine clinical mastitis. MATERIALS AND METHODS: Essential oils were extracted by hydrodistillation technique using Clevenger apparatus. Their chromatographic analysis was performed with a Gas Chromatograph/Mass Spectrometer (GC/MS). Antifungal activities of essential oils were investigated by macrobroth method of dilution in tubes to determine the Minimum Inhibitory Concentrations (MIC 80%). RESULTS: Analysis of the essential oil showed chemical profile dominated by thymol (50.47 and 62.41%) and P-cymene (24.22 and 15.51%) in the oregano and the thyme respectively, 1, 8-cineol (31.50%) and α-pinene (18.33%) in Rosemary. The three essential oils revealed highly effective anticandidal activity, with an MIC of 80% values ranged from 15.02 to 31.08µg/mL. CONCLUSION: These results suggest that essential oils studied can be real alternatives in the control of mastitis fungi but deserving studies more in-depth and detailed on their application in vivo.

Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasis.

Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill's model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole.

Additive action of honey and starch against Candida albicans and Aspergillus niger.

A comparative method of adding honey to culture media with and without starch was used to evaluate the action of starch on the antifungal activity of honey. The minimum inhibitory concentration (MIC) expressed in % (v/v) for two varieties of honey without starch against Candida albicans was 42% and 46%, respectively. For Aspergillus niger the MIC without starch was 51% and 59%, respectively. When starch was incubated with honey and then added to media the MIC for C. albicans was 28% and 38%, respectively, with a starch concentration of 3.6% whereas the MIC for A. niger was 40% and 45%, with a starch concentration of 5.6% and 5.1% respectively. This study suggests that the amylase present in honey increases the osmotic effect in the media by increasing the amount of sugars and consequently increasing the antifungal activity.

Intravesicular administration of clotrimazole for treatment of candiduria in a cat with diabetes mellitus.

A 12-year-old spayed female domestic longhair cat developed fungal cystitis (Candida sp). The cat had a history of chronic diabetes mellitus, hyperadrenocorticism, and bacterial cystitis caused by Escherichia coli. Antifungal agents (itraconazole and fluconazole) were administered orally without noticeable effect on the candiduria. Because of the ineffectiveness of these treatments, intravesicular administration of 1% clotrimazole solution was performed weekly for 3 treatments. Complete resolution of urinary candidiasis was detected after the third infusion. Intravesicular administration of clotrimazole solution appears to be a safe and effective treatment of fungal cystitis in cats.