RESUMO
Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.
Assuntos
Candidíase Vulvovaginal , Nanopartículas , Humanos , Feminino , Camundongos , Animais , Miconazol/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Ácido Hialurônico , Antifúngicos , Candida albicansRESUMO
BACKGROUND: Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. AIMS: Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. METHODS: The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. RESULTS: Curcumin showed minimum inhibitory concentration values of 125-1000µg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. CONCLUSIONS: Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis.
Assuntos
Candidíase Vulvovaginal/tratamento farmacológico , Curcumina/uso terapêutico , Animais , Candida/efeitos dos fármacos , Curcumina/farmacologia , Modelos Animais de Doenças , Feminino , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
Owing to the growing resistance among isolates of Candida species to usual antifungal agents and the well-known therapeutic potential of curcumin, the purpose of this study was to develop and validate a vaginal formulation containing this substance and to evaluating its effectiveness in the treatment of experimental vulvovaginal candidiasis. Curcumin was incorporated in a vaginal cream in three concentrations (0.01%, 0.1% and 1.0%). The different concentrations of the cream and its controls were intravaginally administered in an immunosuppressed rat model to evaluate the efficacy in the treatment of experimental vulvovaginal candidiasis. Samples of the cream were also subjected to centrifugation and physical stability tests and an analytical method for quantification of curcumin was validated based on HPLC. The formulation was stable and the HPLC method could be considered suitable for the quantitative determination of curcumin in the cream. After 6 days of preclinical study, the number of infected animals was 1/6 in all groups treated with curcumin vaginal cream and the fungal burden showed a progressive reduction. Reduction in the inflammatory infiltrate was observed in the group treated with 1.0% cream. Vaginal cream containing curcumin could be considered a promising effective antifungal medicine in the treatment of vulvovaginal candidiasis.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Curcumina/administração & dosagem , Cremes, Espumas e Géis Vaginais/administração & dosagem , Animais , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Centrifugação , Cromatografia Líquida de Alta Pressão , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Estabilidade de Medicamentos , Feminino , Ratos Wistar , Resultado do TratamentoRESUMO
Chemical fractionation of the methanolic extract of leaves of Leiothrix spiralis Ruhland afforded the flavonoids luteolin-6-C-ß-D-glucopyranoside (1), 7-methoxyluteolin-6-C-ß-D-glucopyranoside (2), 7-methoxyluteolin-8-C-ß-D-glucopyranoside (3), 4'-methoxyluteolin-6-C-ß-D-glucopyranoside (4), and 6-hydroxy-7-methoxyluteolin (5), and the xanthones 8-carboxymethyl-1,5,6-trihydroxy-3-methoxyxanthone (6), 8-carboxy-methyl-1,3,5,6-tetrahydroxyxanthone (7). Methanolic extract, fractions, and isolated compounds of the leaves of L. spiralis were assayed against Gram-positive (Staphylococcus aureus, Bacillus subtilis and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella setubal and Helicobacter pylori) and fungi (the yeasts Candida albicans, C. tropicalis, C. krusei and C. parapsilosis). We observed the best minimum inhibitory concentration values for the methanolic extract against Candida parapsilosis, for the fraction 5 + 6 against Gram-negative bacteria E. coli and P. aeruginosa, and compound 7 against all tested Candida strains. The methanolic extract contents suggest that this species may be a promising source of compounds to produce natural phytomedicines.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Metanol/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Anti-Infecciosos/isolamento & purificação , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificaçãoRESUMO
Solanum lycocarpum A. St. Hil. (Solanaceae) is a hairy shrub or small much-branched tree of the Brazilian Cerrado. S. lycocarpum fruits are commonly used in traditional medicine in powder form or as folk preparations for the treatment of diabetes and obesity, as well as for controlling cholesterol levels. The aim of the present study was to chemically characterize the hydroalcoholic extract (SL) of S. lycocarpum by determination of total flavonoids and total poyphenols and quantification of steroidal alkaloids, as well as to evaluate its mutagenic and/or antimutagenic potential on V79 cells and Swiss mice using chromosomal aberrations and bone marrow micronucleus assays, respectively. Three concentrations of SL (16, 32, and 24 µg/mL) were used for the evaluation of its mutagenic potential in V79 cells and four doses (0.25, 0.50, 1.0, and 2.0 g/kg body weight) were used for Swiss mice. In the antimutagenicity assays, the different concentrations of SL were combined with the chemotherapeutic agent doxorubicin (DXR). HPLC analysis of SL gave contents of 6.57â% ± 0.41 of solasonine and 4.60â% ± 0.40 of solamargine. Total flavonoids and polyphenols contents in SL were 0.04 and 3.60â%, respectively. The results showed that not only SL exerted no mutagenic effect, but it also significantly reduced the frequency of chromosomal aberrations induced by DXR in both V79 cells and micronuclei in Swiss mice at the doses tested.