RESUMO
Pullulan (PUL) films containing pomegranate seed oil and Eudragit® RS100 nanocapsules loaded with clotrimazole (CTZ-NC-PUL) were developed to treat vulvovaginal candidiasis (VVC). Our findings showed that the nanocapsule average diameter was around 163 ± 4 nm, with polydispersity index values of up to 0.1 ± 0.01 and positively charged zeta potential (+ 43.5 ± 0.7 mV). The pH was in the acid range (5.14 ± 0.12) and encapsulation efficiency was around 99.6%; CTZ nanoencapsulation promoted higher homogeneity values for the film (91%), and the stability studies displayed no changes in the drug content after 120 days for the CTZ-NC-PUL under refrigerated conditions. All formulations were considered non-irritant, and CTZ-NC-PUL promoted a controlled release of the drug (60% in 24 h) compared to CTZ-PUL (100% in 8 h). The permeation results corroborate the drug release, where higher CTZ amounts were found in the mucosa and receptor medium for CTZ-PUL (21.02 and 4.46 µg/cm2). The films were fast dissolving (10 min), and CTZ-NC-PUL presented higher mucoadhesive properties; the antifungal activity against Candida albicans was maintained, and the in vitro efficacy of the film was proved. In conclusion, CTZ-NC-PUL formulation was considered promising and suitable for vaginal application against candida-related infections.
Assuntos
Candidíase Vulvovaginal , Candidíase , Nanocápsulas , Feminino , Humanos , Gravidez , Clotrimazol/farmacologia , Clotrimazol/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Candida albicans , Candidíase/tratamento farmacológico , Parto ObstétricoRESUMO
This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.
Assuntos
Aromatase/metabolismo , Clotrimazol/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Endometriose/tratamento farmacológico , Endométrio/efeitos dos fármacos , Estrogênios/sangue , Animais , Clotrimazol/farmacologia , Modelos Animais de Doenças , Endometriose/metabolismo , Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Ratos , Ratos WistarRESUMO
The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200â¯mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group. The treatment also promotes a reduction on PGE2 and TNF-α levels. All these effects involve the amelioration of ERK1/2, Akt, AMPK and PERK signaling upon CTZ treatment. In conclusion, CTZ promoted an overall amelioration of endometriosis in a rat model due to the anti-angiogenic properties of the drug. Therefore, our results support the proposal of a clinical trial using CTZ for the treatment of endometriosis.
Assuntos
Clotrimazol/uso terapêutico , Endometriose/tratamento farmacológico , Endométrio/patologia , Próteses e Implantes , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clotrimazol/efeitos adversos , Clotrimazol/farmacologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Endometriose/patologia , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Feminino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Ratos WistarRESUMO
PURPOSE: To demonstrate non-inferiority of eberconazole 1% otic solution to clotrimazole 1% solution, and to compare their safety profiles in the treatment of otomycosis. MATERIALS AND METHODS: Multicenter, randomized, double-blind, active treatment-controlled phase 3 clinical trial. One hundred and ninety patients with diagnosis of otomycosis were randomly assigned to eberconazole 1% otic solution or clotrimazole 1% solution. RESULTS: Baseline characteristics were comparable between both groups for age, gender, ethnicity, and clinical variables. Both study groups had high complete response rates: 81.8% in the eberconazole group and 83.5% in the clotrimazole group. Although non-inferiority of eberconazole relative to clotrimazole could not be demonstrated, a post-hoc sensitivity analysis demonstrated that eberconazole 1% otic solution was not inferior to clotrimazole 1% solution for the primary efficacy endpoint. Secondary endpoints also demonstrated that eberconazole 1% and clotrimazole 1% solutions were therapeutically similar at the end of the study. The incidence of adverse events was similar in both groups, and none had related AEs and withdrawals due to an AE. CONCLUSIONS: Eberconazole 1% otic solution is an efficacious and safe option to treat otomycosis-affected patients in the general practice.
Assuntos
Antifúngicos/uso terapêutico , Clotrimazol/uso terapêutico , Cicloeptanos/uso terapêutico , Imidazóis/uso terapêutico , Otomicose/tratamento farmacológico , Administração Tópica , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Otomicose/microbiologia , Otomicose/fisiopatologia , Segurança do Paciente , Soluções/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Superficial fungal infections are among the most commonly managed skin problems by general practitioners. Although evidence shows combination antifungal/corticosteroid topicals are more expensive and less effective than single-agent antifungals, practitioners continue to prescribe combination agents. We examined current prescription trends of 2 combination antifungal/corticosteroid medications, Lotrisone and Mycolog-II.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Betametasona/uso terapêutico , Clotrimazol/uso terapêutico , Dermatomicoses/tratamento farmacológico , Glucocorticoides/uso terapêutico , Gramicidina/uso terapêutico , Neomicina/uso terapêutico , Nistatina/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Adolescente , Criança , Pré-Escolar , Combinação de Medicamentos , Humanos , Lactente , Recém-Nascido , Padrões de Prática MédicaRESUMO
Previous clinical studies have demonstrated the antifungal effectiveness of Ageratina pichinchensis extracts when topically administered to patients with dermatomycosis. The objective of this study was to evaluate the effectiveness and tolerability of a 7% standardized extract of A. pichinchensis (intravaginal) in patients with vulvovaginal candidiasis. The extract was standardized in terms of its encecalin content and administered during 6 days to patients with Candida albicans-associated vulvovaginitis. The positive control group was treated with Clotrimazole (100 mg). On day 7 of the study, a partial evaluation was carried out; it demonstrated that 94.1% of patients treated with Clotrimazole and 100% of those treated with the A. pichinchensis extract referred a decrease or absence of signs and symptoms consistent with vulvovaginal candidiasis. In the final evaluation, 2 weeks after concluding administration, 86.6% of patients in the control group and 81.2% (p = 0.65) of those treated with the A. pichinchensis extract demonstrated therapeutic success. Statistical analysis evidenced no significant differences between the two treatment groups. With the results obtained, it is possible to conclude that the standardized extract from A. pichinchensis, intravaginally administered, showed therapeutic and mycological effectiveness, as well as tolerability, in patients with vulvovaginal candidiasis, without noting statistical differences in patients treated with Clotrimazole. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Ageratina/química , Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adulto , Candida albicans/efeitos dos fármacos , Clotrimazol/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Fitoterapia/métodos , Projetos Piloto , Resultado do TratamentoAssuntos
Ascomicetos/isolamento & purificação , Dermatomicoses/microbiologia , Dermatoses do Pé/microbiologia , Doença Relacionada a Viagens , Antifúngicos/uso terapêutico , Clotrimazol/uso terapêutico , Colômbia , Dermatomicoses/tratamento farmacológico , Doenças Endêmicas , Feminino , Dermatoses do Pé/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Espanha/epidemiologia , Terbinafina , Dedos do PéRESUMO
OBJECTIVE: To study Candida albicans genotypes using RAPD and their susceptibility to fluconazole in healthy pregnant women and in vulvovaginal candidiasis (VVC) patients after topical treatment with clotrimazole. METHODS: Vaginal swabs were collected at t = 0 and t = 1 (1 month later) in pregnant women (control group, n = 33), and before (t = 0), at 1 month (t = 1) and at 2 months (t = 2) after clotrimazole treatment in pregnant women with VVC. RESULTS: Candida albicans was isolated in 30% of healthy pregnant women and 80% of patients with VVC. A high genetic heterogeneity was observed in C. albicans genotypes between individuals. In patients with VVC, topical antifungal treatment with clotrimazole was clinically effective, but only in a 62% C. albicans was eradicated. In patients in which C. albicans was not eradicated, this microorganism persisted for 1 or 2 months after the antifungal treatment. The persistent colonies were not associated with a specific genotype, but they were associated with higher MICs in comparison with colonies isolated from the control group. CONCLUSIONS: Therapy with topical clotrimazole, despite a good clinical outcome, could not eradicate completely C. albicans allowing the persistence of genotypes, with higher MICs to fluconazole. More studies with higher number of patients are needed to validate this preliminary finding.
Assuntos
Candida albicans/classificação , Candida albicans/genética , Candidíase Vulvovaginal/microbiologia , Genótipo , Técnicas de Genotipagem , Complicações Infecciosas na Gravidez/microbiologia , Administração Tópica , Adolescente , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Clotrimazol/uso terapêutico , Feminino , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Técnica de Amplificação ao Acaso de DNA Polimórfico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles. METHODOLOGY/PRINCIPAL FINDINGS: Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231) that present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake in all three cell lines, with K(i) values of 114.3±11.7, 77.1±7.8 and 37.8±4.2 µM for MCF10A, MCF-7 and MDA-MB-231, respectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes, hexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this last cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7 and MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on MDA-MB-231. CONCLUSIONS/SIGNIFICANCE: Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism, growth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents little or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that the more aggressive the cell is the more effective clotrimazole is.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Clotrimazol/farmacologia , Glicólise/efeitos dos fármacos , Antineoplásicos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clotrimazol/uso terapêutico , Feminino , Humanos , MetabolomaRESUMO
La candidiasis orofaríngea (COF) permanece como una de las principales infecciones oportunistas en pacientes infectados con el virus de la inmunodeficiencia humana (VIH) y con el síndrome de inmunodeficiencia adquirida (sida), y aunque su incidencia ha disminuido con la introducción de la terapia antirretroviral de alta eficacia, continúa siendo una afección característica en estos pacientes. En el presente trabajo se realizó un estudio de susceptibilidad in vitro mediante la metodología del CLSI, frente a itraconazol, ketoconazol y clotrimazol de 144 aislamientos clínicos de Candida, aisladas de la cavidad oral de pacientes infectados con el VIH/sida con cuadros clínicos de COF. La identificación de los aislamientos demostró que más del 90% pertenecían a Candida albicans. Al determinar el patrón general de susceptibilidad frente a los azoles estudiados mediante el método de microdilución en caldo del documento M27-A2 del Clinical and Laboratory Standard Institute, C. albicans exhibió valores de concentración mínima inhibitoria (CMI) en un rango de 0,01 a 8µg/mL para el itraconazol y el ketoconazol y de 0,01 a 2 g/mL para el clotrimazol. Sólo el 2,1 % de los aislamientos mostró franca resistencia frente al itraconazol, en tanto que el 3,5 % quedó clasificado dentro de la categoría susceptible dosis-dependiente para este triazol. La mayoría de los aislamientos de C. albicans mostraron valores de CMI frente al ketoconazol y al clotrimazol menores a 0.06 g/mL, siendo de un 96,9% (129 aislamientos) y de un 97,7% (129 aislamientos), respectivamente. El clotrimazol tuvo una mejor actividadin vitro comparado con los restantes azoles frente a los aislamientos estudiados. Candida spp. Mostró una elevada sensibilidad in vitro a los azoles estudiados. Se hace necesario continuar realizando estudios epidemiológicos para determinar los patrones de susceptibilidad y tasas de resistencias frente a los agentes...
The oropharyngeal candidiasis (OFC) remains as one of the principal opportunistic infections in patients infected with the human immunodeficiency virus (HIV) and with the acquired immunodeficiency syndrome (aids), and although his incidence has declined with the introduction of the highly active anti-retroviral therapy (HAART), remains as a typical complaint in these patients. A study of antifungal in vitro susceptibility testing, following the CLSI methodology, was realized against itraconazole, ketoconazole and clotrimazole of 144 clinical isolations of Candida, isolated from the oral cavity of patients infected with HIV/aids, with clinical pictures of OFC. The isolations identification, demonstrated that more than 90% belonged to Candida albicans. The determination of the general pattern of susceptibility, following the document M27-A2 of the Clinical and Laboratory Standard Institute, against to the studied azoles by means of the method of microdilution in liquid medium, show that the majority of C. albicans isolates showed values of MIC against ketoconazole and clotrimazole lower than 0.06 g/mL, representing a 96,9% (129 isolations) and a 97,7% (129 isolations), respectively. C. albicans exhibited the widest range of minimal inhibitory concentration (MIC). Only 2.1% of the isolations showed resistance against to itraconazole, while 3.5 % remained classified in the category sensible dose - dependent for this triazole. The majority of the strains showed values of MIC against ketoconazole and clotrimazole below 0.06 g/mL. The clotrimazole had a better in vitro activity compared with the remaining azoles opposite to the isolations. Candida spp. showed a high in vitro sensibility to the azoles studied. It becomes necessary the maintenance of epidemiologic studies for the determination of susceptibility patterns and of resistances rates against to the antifungal agents