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  • Title: Development, characterization, and in vitro-in vivo evaluation of polymeric nanoparticles containing miconazole and farnesol for treatment of vulvovaginal candidiasis.
    Author: Fernandes Costa A, Evangelista Araujo D, Santos Cabral M, Teles Brito I, Borges de Menezes Leite L, Pereira M, Correa Amaral A.
    Journal: Med Mycol; 2019 Jan 01; 57(1):52-62. PubMed ID: 29361177.
    Abstract:
    Vulvovaginal candidiasis (VVC) is caused mainly by the opportunistic fungus Candida albicans, and its yeast to hyphae transition is considered a major virulence factor. Farnesol is a molecule that inhibits yeast to hyphae transition. The increased incidence of VVC has influenced a need for developing new therapeutic strategies. The objective was to develop a mucoadhesive nanostructured system composed of miconazole and farnesol co-encapsulated within chitosan nanoparticles. The miconazole presented a minimal inhibitory concentration (MIC) of 1 μg/ml against C. albicans. The farnesol was capable of inhibiting yeast to hyphae transition at levels greater or equal to 300 μM. The combination of miconazole and farnesol showed no change in miconazole MIC. Chitosan nanoparticles containing miconazole and farnesol were prepared by ionic gelation and showed favorable characteristics for use on mucous membranes. They showed size variation and polydispersion index (PDI) after 30 days, but the efficiency of drug encapsulation was maintained. Regarding toxicity in cultured fibroblasts (BALB/c 3T3) the nanoparticles were considered nontoxic. The nanoparticles showed antifungal activity against the C. albicans strain used with MICs of 2.5 μg/ml and 2 μg/ml for nanoparticles containing miconazole or miconazole/farnesol, respectively. Nanoparticles containing farnesol inhibited yeast to hyphae transition at concentrations greater than or equal to 240 μM. The in vivo antifungal activity was assessed in the murine model for VVC. The results suggested that chitosan nanoparticles containing miconazole and farnesol were effective at inhibiting fungal proliferation. Additionally, chitosan nanoparticles containing farnesol were capable of decreasing the pathogenicity of infection, demonstrated through the absence of inflammation.
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