Chitosan nanoparticles encapsulating farnesol evaluated in vivo against Candida albicans.

Farnesol is a natural essential oil with antimicrobial properties. Complexation of farnesol in chitosan nanoparticles can be useful to improve its bioavailability and potentiate its antifungal capabilities such as inhibition of hyphal and biofilm formation. The aim of this study was to develop and characterize chitosan nanoparticles with farnesol (NF) and evaluate their toxicity and antifungal action on C. albicans in vivo. The NF were prepared by the ionic gelation method and showed physicochemical characteristics such as diameter less than 200 nm, monodisperse distribution, positive zeta potential, spherical morphology, and stability after 120 days of storage. In the evaluation of toxicity in Galleria mellonella, NF did not reduce the survival rate, indicating that there was no toxicity in vivo at the doses tested. In the assays with G. mellonella infected by C. albicans, the larvae treated with NF had a high survival rate after 48 h, with a significant reduction of the fungal load and inhibition of the formation of biofilms and hyphae. In the murine model of vulvovaginal candidiasis (VVC), histopathological analysis showed a reduction in inflammatory parameters, fungal burden, and hyphal inhibition in mice treated with NF. The produced nanoparticles can be a promising alternative to inhibit C. albicans infection.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

HPLC Method Validated for Quantification of Fluconazole Co-Encapsulated with Propolis Within Chitosan Nanoparticles.

Considering the cases of fungal resistance to classic antifungals, it is necessary to develop more efficient and innovative therapies capable of reversing this situation. Fluconazole is an antifungal frequently used in the treatment of mycosis and some fungi developed resistance to its mechanism of action. In this work, fluconazole and green propolis were co-encapsulated in chitosan nanoparticles to be explored in order to promote a synergistic effect to enhance its therapeutic efficacy. However, because of the complexity of the chemical composition of green propolis, it was necessary to develop a simple and precise methodology to quantify fluconazole in the formulation. High Efficiency Liquid Chromatography methodology was developed and validated following the Brazilian regulatory guidelines (ANVISA, RDC 166/2017) for the separation of co-eluted peaks of fluconazole and green propolis in the nanoparticle supernatant. Applying the method developed, it was possible to quantify fluconazole in the same sample containing propolis. Thus, the results allow to affirm that it is a specific test, effective, precise and robust, which helped to determine the efficiency of association of the compounds within the nanoparticle. The method can be applied to quantify compounds that have similar chromatographic retention times. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00954-2.