RESUMO
Drug repositioning has been an important ally in the search for new antifungal drugs. Statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are promissory candidates to be repositioned to treat mycoses. In this study we evaluated the antifungal activity of atorvastatin by in vitro tests to determine the minimum inhibitory concentration against azole resistant Candida albicans and its mechanisms of action. Moreover, the efficacy of both atorvastatin-loaded oral and vaginal emulgels (0.75%, 1.5% and 3% w/w) was evaluated by means of in vivo experimental models of oral and vulvovaginal candidiasis, respectively. The results showed that atorvastatin minimal inhibitory concentration against C. albicans was 31.25 µg/ml. In oral candidiasis experiments, the group treated with oral emulgel containing 3.0% atorvastatin showcased total reduction in fungal load after nine days of treatment. Intravaginal delivery atorvastatin emulgel showed considerable effectiveness at the concentration of 3% (65% of fungal burden reduction) after nine days of treatment. From these findings, it is possible to assert that atorvastatin may be promising for drug repositioning towards the treatment of these opportunistic mycoses.
Atorvastatin is a statin drug that presents antifungal activity. This study showed that atorvastatin-containing oral and vaginal emulgels were able to treat vulvovaginal and oral candidiasis of infected animal model. Therefore, we showcased that atorvastatin may be a possible therapeutic agent in order to be a used to control opportunistic mucosal fungal infections caused by Candida albicans.
Assuntos
Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Vulvovaginal/tratamento farmacológico , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Azóis/farmacologia , Candidíase Bucal/microbiologia , Candidíase Vulvovaginal/microbiologia , Modelos Animais de Doenças , Reposicionamento de Medicamentos , Farmacorresistência Fúngica , Feminino , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Ratos , Resultado do TratamentoRESUMO
Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 µg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 µg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC.
Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Eriocaulaceae/química , Nanoestruturas/química , Extratos Vegetais/uso terapêutico , Animais , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Candidíase Vulvovaginal/microbiologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Extratos Vegetais/química , Ratos , Ratos WistarRESUMO
Vulvovaginal candidiasis, mostly caused by Candida albicans, remains a prevalent concern in women's health. Annona muricata L. (Annonaceae), a plant native from Brazil, is well-known for its therapeutic potential, including antitumor, anti-inflammatory, and antimicrobial properties. This study presents an innovative hydrogel formulation containing the ethanolic extract from A. muricata leaves designed to control C. albicans in an in vivo model of vulvovaginal candidiasis. Here, we report the development, thermal, physicochemical and rheological characterization of a Carbopol®-based hydrogel containing A. muricata extract. Furthermore, we evaluated its activity in a vulvovaginal candidiasis in vivo model. Thermal analyses indicated that the addition of the extract increased the polymer-polymer and polymer-solvent interactions.Rheological analysis showed a decrease in the viscosity and elasticity of the formulation as the A. muricata extract concentration increased, suggesting a liquid-like behavior. After treatment with the Carbopol®-based hydrogel with A. muricata, our in vivo results showed a significant reduction in vulvovaginal fungal burden and infection, as well as a reduction in mucosal inflammation. The current research opens up possibilities for the application of the Carbopol®-based hydrogel with A. muricata as a natural therapeutic option for the treatment of vulvovaginal candidiasis.
Assuntos
Annona , Antifúngicos , Candida albicans , Candidíase Vulvovaginal , Hidrogéis , Extratos Vegetais , Folhas de Planta , Annona/química , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Antifúngicos/farmacologia , Antifúngicos/química , Feminino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Hidrogéis/química , Hidrogéis/farmacologia , Candida albicans/efeitos dos fármacos , Animais , Reologia , Testes de Sensibilidade Microbiana , CamundongosRESUMO
The purpose of this study was to evaluate the in vitro anticandidal activity of a methanolic extract of Syngonanthus nitens scapes against different Candida species and clinical isolates from patients with vulvovaginal candidiasis (VVC), and its effect in vivo in the treatment of vaginal infection. Chemical characterization of the extract was performed by HPLC-UV analyses and showed the presence of flavones derivatives. The extract was effective against several Candida strains from our collection and species recovered from VVC patients, and was able to inhibit the yeast-hyphal transition. No cytotoxic activity against human female reproductive tract epithelial cells and no hemolytic activity against human red blood cells were observed. In the in vivo model of VVC, we evaluated the efficacy of the intravaginal treatment with a cream containing the extract at doses of 0.5, 1.0 and 2.0%. The treatment eradicated the vaginal fungal burden in infected rats after 8 days of treatment. S. nitens extract could be considered as an effective and non-toxic natural antifungal agent in the treatment of vulvovaginal candidiasis.
Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Eriocaulaceae/química , Extratos Vegetais/uso terapêutico , Administração Tópica , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Candida/isolamento & purificação , Candidíase Vulvovaginal/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Flavonas/isolamento & purificação , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonas/toxicidade , Humanos , Testes de Sensibilidade Microbiana , Pomadas/uso terapêutico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Espectrofotometria Ultravioleta , Resultado do TratamentoRESUMO
ETNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Annona muricata L. (soursop) include treatment for cancer, fungal infections, and inflammatory diseases. Its phytoconstituents, mainly acetogenins and alkaloids, are associated with therapeutic activity and clinical application is currently under investigation. However, the application of phytotherapy to treat diseases caused by fungal biofilms, such as vulvovaginal candidiasis (VVC), is still limited. AIM OF THE STUDY: To investigate the activity of the ethanolic extract of A. muricata leaves (AML) against biofilms formed by multiresistant Candida albicans (ATCC® 10231) both in vitro and in a VVC experimental model. MATERIAL AND METHODS: C. albicans biofilms were grown and their adhesion, proliferation, development, and matrix composition studied by spectrophotometry, scanning electron microscopy (SEM), whole slide imaging (WSI), and biochemical assays without or with AML treatment. In parallel, in vivo experiments were conducted using a murine model of infection treated with different concentrations of the extract and nystatin. Fungal burden and histological changes were investigated. RESULTS: The proliferation and adhesion of C. albicans biofilms were significantly reduced as confirmed by SEM and WSI quantitative analyses. Furthermore, the concentration of carbohydrates, proteins and DNA was reduced in the biofilm matrix. In vivo assays demonstrated that AML was able to reduce the fungal burden and the inflammatory process. CONCLUSIONS: The findings further emphasized the therapeutic and scientific potential of AML, thus encouraging its future use in the treatment of VVC.
Assuntos
Annona , Candidíase Vulvovaginal , Leucemia Mieloide Aguda , Humanos , Feminino , Animais , Camundongos , Candida albicans , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Biofilmes , Etanol/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
The biological activities of a plant extract depend on a complex sum of individual properties including the antioxidant activity. Several biological activities protect against the harmful action of reactive oxygen species (ROS), and here we focused our attention on the relationship between the biological activities tested and the antioxidant properties. In this study, the total flavonoid content as well as the antioxidant, antimicrobial, hemolytic and cytotoxicity activities of the methanolic extract of Leitothrix spiralis leaves were evaluated. The extract showed a total flavonoid content of 19.26% and the chemical characterization by HPLC-PAD confirmed the presence of flavonoids as the major secondary metabolite compounds. Significant antioxidant activity (IC(50) = 1.743 µg/mL ± 0.063) was demonstrated and was effective against Gram-negative organisms and all Candida strains tested, and showed an ability to inhibit hyphal formation. Non-hemolytic and antiproliferative activity could be demonstrated.
Assuntos
Antioxidantes/farmacologia , Candida albicans/crescimento & desenvolvimento , Eriocaulaceae/química , Bactérias Gram-Negativas/crescimento & desenvolvimento , Hemólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antioxidantes/química , Eritrócitos/citologia , Eritrócitos/metabolismo , Células HeLa , Humanos , Extratos Vegetais/químicaRESUMO
The treatment of vulvovaginal candidiasis (VVC) is based on oral and vaginal formulations which show limited effectiveness. In this study, amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) were developed to overcome the drawbacks of the conventional formulations. AMP EUD nanoparticles/HA were synthesized by nanoprecipitation, formulated by statistical experimental design, and characterized. AMP release from EUD nanoparticles/HA and its antifungal activity in a murine model of VVC were evaluated. Nanoparticles showed 147.6⯱â¯16.7â¯nm of diameter, 0.301⯱â¯0.09 of polydispersity index, - 29.9⯱â¯3.76â¯mV of zeta potential, and 87.27 % of encapsulation efficiency. They released about 81 % of AMP in 96â¯h; and provided the elimination of 100 % of the vaginal fungal burden in 24â¯h. It was suggested that the AMP EUD nanoparticles/HA penetrated into the vaginal epithelium via CD44 receptors. These AMP EUD nanoparticles/HA represent a non-conventional vaginal formulation to improve the treatment of VVC.
RESUMO
Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.
Assuntos
Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Quitosana , Extratos Vegetais/administração & dosagem , Rubiaceae/química , Cremes, Espumas e Géis Vaginais/administração & dosagem , Antifúngicos/química , Fenômenos Químicos , Quitosana/química , Relação Dose-Resposta a Droga , Feminino , Humanos , Extratos Vegetais/química , Cremes, Espumas e Géis Vaginais/químicaRESUMO
Vulvovaginal candidiasis is an inflammation localized in the vulvovaginal area. It is mostly caused by Candida albicans. Its treatment is based on the systemic and local administration of antifungal drugs. However, this conventional therapy can fail owing to the resistance of the Candida species and noncompliance of patients. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers are single-use, antifungal, controlled drug delivery systems, and represent an alternative therapeutic scheme for the local treatment of vulvovaginal candidiasis. Nanofibers were characterized by analytical techniques and with an in vitro drug delivery study. In vitro and in vivo fungicidal activity of amphotericin B released from nanofibers was evaluated using the agar diffusion method and an experimental murine model of vulvovaginal candidiasis, respectively. Analytical techniques showed that amphotericin B was physically mixed in the polymeric nanofibers. Nanofibers controlled the delivery of therapeutic doses of amphotericin B for 8 consecutive days, providing effective in vitro antifungal activity and eliminated the in vivo vaginal fungal burden after 3 days of treatment and with only one local application. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers could be potentially applied as an alternative strategy for the local treatment of vulvovaginal candidiasis without inducing fungal resistance, yet ensuring patient compliance.