Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 574
Filtrar
1.
J Pharm Sci ; 110(11): 3702-3714, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34293406

RESUMO

Econazole nitrate, an antifungal drug used in the handling of skin ailments, is commercially not efficient as these ailments typically require a more elevated concentration of the drug to offer an effective pharmacological retort. Like so, it is proposed to assess the effectiveness of the topical hydrogel of econazole-loaded nanosponge in the management of skin ailment(s). Econazole nitrate-laden ß-cyclodextrin nanosponges were developed by employing the melt method using ß-cyclodextrin as the organic polymer and N,N-carbonyldiimidazole as the crosslinker. The critical factors disturbing the quality of the formulation were uniquely identified by the Ishikawa diagram, and they were optimized by the statistical experiment design concept. ß-cyclodextrin loaded nanosponges were uniquely designed using the Placket-Burman approach and optimized utilizing the Box-Behnken method. The optimized nanosponges (EN-CDN) were  421.37 ± 6.19 nm in size with an entrapment efficiency of 70.13% ± 5.73%. The topical hydrogel of nanosponges (EN-TG) was prepared using carbopol 934 and pyrrolidone as permeation enhancers. In vitro skin permeation studies affirmed the improved transport crosswise the goatskin for topical hydrogel in comparison to the marketed product. EN-TG was able to control the fungal infection in the selected animal model in comparison to the marketed preparation. Stability studies reported favorably that nanogel remained stable under normal and accelerated settings.


Assuntos
Econazol , beta-Ciclodextrinas , Animais , Antifúngicos , Portadores de Fármacos , Hidrogéis , Pele
2.
Mymensingh Med J ; 30(3): 638-643, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226449

RESUMO

Fungal infection of the ear canal is called Otomycosis. It is more common in hot and humid condition. There are many modalities of treatment or therapeutic agent for treatment of otomycosis. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream is a topical antifungal agent described to be effective in the treatment of otomycosis. This study was performed to compare the efficacy of topical application clotrimazole 1% solution and Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream in the treatment of otomycosis. A controlled, randomized and open clinical trial was carried out in ENT department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2020 to July 2020. Patients diagnosed with fungal otitis externa who were treated with topical antifungals were included in this study. They were randomized into two treatment groups: i) Clotrimazole 1% solution, 2) Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream. Patients were microscopically evaluated at two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed, follow up and final outcomes (absence of infection) were compared between two groups. One hundred & two (102) patients were included, 51 in the clotrimazole 1% solution group and 51 in the Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group. Predominant symptoms are pain, pruritus, aural fullness and hearing loss. Aspergillus organism was isolated most frequently (63.73%). Treatment with clotrimazole 1% solution groups resulted in 88.23% resolution vs. 80.39% resolution with Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream at 2 weeks of treatment. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group demonstrated higher treatment failure 11.76 and 19.60 respectively. Clotrimazole 1% solution is more effective than Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream for uncomplicated otomycosis. More study is needed to corroborate our results.


Assuntos
Econazol , Otomicose , Administração Tópica , Antifúngicos/uso terapêutico , Bangladesh , Clotrimazol/uso terapêutico , Econazol/uso terapêutico , Humanos , Otomicose/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico
3.
Laryngoscope ; 131(5): E1640-E1646, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33141477

RESUMO

OBJECTIVES/HYPOTHESIS: To compare the efficacy and adverse effects of triamcinolone acetonide econazole cream and nystatin suspension in the treatment of otomycosis, and to determine the clinical features, predisposing factors, and etiology of otomycosis. STUDY DESIGN: A prospective study. METHODS: A prospective clinical trial was conducted on 786 patients diagnosed with otomycosis. The study population was randomly divided into two treatment groups of triamcinolone acetonide econazole cream (TAEC) and nystatin suspension in a 1:1 ratio. After clearing all fungal deposits in the external auditory canal, the antimycotic drugs were locally applied for at least 2 weeks. The efficacy and adverse effects were compared between the two antifungal reagents by statistical analysis. Meanwhile, patient clinical data were collected to find out the clinical features, predisposing factors, and etiology. RESULTS: Pruritis was the most common symptom and Aspergillus niger was the leading fungal pathogen. There was high association (44.5%) of otomycosis with a history of unclean ear picking. The cure rate was 97.6% in the TAEC group and 73.5% in the nystatin group (P < .01). Treatment with TAEC resulted in 2.4% of patients complaining of discomforts (irritant dermatitis, otalgia, or headache) versus 59.8% of patients complaining discomforts treated with nystatin (P < .01). The residue rate of antifungals was 1.9% in the TAEC group and 89.9% in the nystatin group (P < .01) at the end of treatment. CONCLUSIONS: Thoroughly cleaning of the external auditory canal followed by local use of TAEC under endotoscope is an effective, convenient, and well-tolerated treatment for otomycosis. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:E1640-E1646, 2021.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Econazol/administração & dosagem , Nistatina/administração & dosagem , Otomicose/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Aspergilose/diagnóstico , Aspergilose/microbiologia , Aspergillus niger/isolamento & purificação , Criança , Pré-Escolar , Dermatite Irritante/epidemiologia , Dermatite Irritante/etiologia , Combinação de Medicamentos , Meato Acústico Externo/efeitos dos fármacos , Meato Acústico Externo/microbiologia , Dor de Orelha/induzido quimicamente , Dor de Orelha/epidemiologia , Econazol/efeitos adversos , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nistatina/efeitos adversos , Otomicose/microbiologia , Estudos Prospectivos , Suspensões , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos , Adulto Jovem
4.
Int J Pharm ; 591: 119979, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068694

RESUMO

Several strategies have been explored to obtain effective econazole nitrate (ECN) concentrations at the site of application for a prolonged time. In this paper, different gelatin-based film formulations for vaginal application were investigated, containing ECN (10% w/w with respect to gelatin) as pure drug or as drug-solid dispersions (SD). For the production of SD, different polymers were evaluated: polyvinylpyrrolidone (PVP), Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and Gelucire® 50/13 (mixture of mono-, di- and triglycerides of fatty acids, esters of PEG 1500 and free PEG). Gelucire®-SD showed the best solubility enhancement, increasing 9.2 times the ECN solubility in pH 4.5 solution respect to pure drug; DSC and XRD analysis confirmed the crystalline form of the drug. XRD results evidenced that all gelatin-based films, containing either the drug or the SD, underwent the topotactic transformation of ECN into crystalline econazole (EC), owing to a strong interaction between the drug and the gelatin. Films containing Gelucire®-based SD displayed lower brittleness and rigidity with respect to the other samples; moreover they demonstrated good structural integrity after 24 h of incubation in the acidic solution (swelling degree of about 350%). Then, Gelucire®-SD based films were compared with the corresponding formulations cross-linked by genipin (2% w/w). The addition of genipin did not interfere with the drug-gelatin interaction. Gelucire®-SD based films showed similar release profiles to neat gelatin films, enhancing the drug release in the first 5 h and controlling the EC release over time, avoiding the use of a crosslinking additive. Finally, gelatin films containing Gelucire® solid dispersion displayed good adhesiveness and anti-Candida activity. Overall, results support the potential use of this film formulation as noncytotoxic EC delivery system for the treatment of vaginal candidiasis.


Assuntos
Econazol , Gelatina , Parto Obstétrico , Feminino , Humanos , Polietilenoglicóis , Gravidez , Solubilidade
5.
Am J Trop Med Hyg ; 103(5): 2127-2128, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32901593

RESUMO

Trichophyton tonsurans is an anthropophilic dermatophyte with a worldwide distribution and is responsible for superficial mycosis with a wide range of clinical manifestations. We report two atypical cases of tinea due to T. tonsurans in two children: a case of extensive tinea corporis and a case of inflammatory tinea capitis.


Assuntos
Antifúngicos/administração & dosagem , Econazol/administração & dosagem , Griseofulvina/administração & dosagem , Inflamação/diagnóstico , Tinha do Couro Cabeludo/diagnóstico , Trichophyton/isolamento & purificação , Adolescente , Criança , Humanos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/patologia , Masculino , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/patologia
6.
Anal Biochem ; 602: 113791, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473119

RESUMO

Econazole is a widely used chiral antifungal drug. In this paper, an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of econazole enantiomers in rat plasma for the first time. After addition of the internal standard (IS) clotrimazole, plasma samples were extracted by liquid-liquid extraction with n-hexane:2-propanol (98.5:1.5, v/v). Baseline separation of the enantiomers was achieved on a Chiralpak® IC column (250 mm × 4.6 mm, 5 µm) using acetonitrile-ammonium acetate buffer (5 mM) (85:15, v/v) as mobile phase. The detection of the analytes was performed in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 381.07 â†’ 124.92 and 276.78 â†’ 164.92 were monitored for econazole enantiomers and clotrimazole, respectively. The linear range was 0.20-50.00 ng/mL with the lower limit of quantification of 0.20 ng/mL for both econazole enantiomers in plasma. The intra-day and inter-day precisions were not exceeding 10.2% and the accuracies were within ±15.0%. The validated method was successfully applied to the stereoselective pharmacokinetic study of econazole enantiomers in rat plasma after transdermal administration of racemic econazole nitrate cream. Significant differences were observed in Cmax, AUC and CL/F of econazole enantiomers, indicating the enantioselective pharmacokinetic behavior of econazole in rats.


Assuntos
Econazol/sangue , Econazol/farmacocinética , Administração Cutânea , Animais , Econazol/química , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Estereoisomerismo , Distribuição Tecidual
7.
J Chromatogr A ; 1621: 461085, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32376018

RESUMO

Two analytical methodologies based on the combined use of hydroxypropyl-ß-cyclodextrin and two different amino acid-based chiral ionic liquids (tetrabutylammonium-L-lysine or tetrabutylammonium-L-glutamic acid) in electrokinetic chromatography were developed in this work to perform the enantioselective determination of econazole and sulconazole in pharmaceutical formulations. The influence of different experimental variables such as buffer concentration, applied voltage, nature and concentration of the ionic liquid, temperature and injection time, on the enantiomeric separation was investigated. The combination of hydroxypropyl-ß-cyclodextrin and tetrabutylammonium-L-lysine under the optimized conditions enabled to achieve the enantiomeric determination of both drugs with high enantiomeric resolution (3.5 for econazole and 2.4 for sulconazole). The analytical characteristics of the developed methodologies were evaluated in terms of linearity, precision, LOD, LOQ and recovery showing good performance for the determination of both drugs which were successfully quantitated in pharmaceutical formulations. This work reports the first analytical methodology enabling the enantiomeric determination of sulconazole in pharmaceutical formulations.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Cromatografia Capilar Eletrocinética Micelar/métodos , Econazol/análise , Ácido Glutâmico/química , Imidazóis/análise , Líquidos Iônicos/química , Lisina/química , Compostos de Amônio Quaternário , Estereoisomerismo , Temperatura , Fatores de Tempo
8.
Infect Dis Obstet Gynecol ; 2020: 7201840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410819

RESUMO

Purpose: A novel fixed-dose combination of 150 mg of econazole with 6 mg of benzydamine formulated in vaginal ovules was investigated in a randomised, double-blind, four-parallel group, tolerability, and pharmacokinetic Phase I study in healthy women. Methods: The fixed-dose combination was compared to econazole and benzydamine single-drug formulations and with placebo after daily applications for 3 consecutive days. Safety and tolerability were evaluated recording the adverse drug reactions, local and general tolerability scores, clinical laboratory assays, and vital signs. Econazole, benzydamine, and its metabolite benzydamine N-oxide pharmacokinetics were investigated after single and multiple applications. Results: Local reactions were generally absent. Pruritus and pain at the application site were infrequently reported. According to the subjects' evaluations, the overall tolerability of the ovules was rated as excellent or good. No significant effect of any treatment on laboratory parameters, vital signs, body weight, vaginal pH, or ECG was observed. Very low econazole, benzydamine, and benzydamine-N-oxide concentrations were measured in plasma, though quantifiable in almost all samples. Conclusion: The tested fixed-dose combination showed a good safety profile consistently with the known tolerability of both active substances. In addition, the confirmed low bioavailability of the drugs excludes the possibility of any accumulation effects and limits the risk of undesired systemic effects. This trial is registered at ClinicalTrials.gov with the identifier NCT02720783 last updated on 07 February 2017.


Assuntos
Antifúngicos/farmacocinética , Benzidamina/farmacocinética , Sistemas de Liberação de Medicamentos/instrumentação , Econazol/farmacocinética , Vagina/efeitos dos fármacos , Administração Oral , Adulto , Antifúngicos/administração & dosagem , Área Sob a Curva , Benzidamina/administração & dosagem , Benzidamina/análogos & derivados , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Econazol/administração & dosagem , Feminino , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Adulto Jovem
9.
Int J Pharm ; 580: 119229, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32184178

RESUMO

The study aims to assess the ultrasound-assisted econazole nitrate (EN) permeation from topically applied formulations with potential for treating Raynaud's phenomenon. Optimization of ultrasound parameters such as the distance of the horn, application time and amplitude were performed. In vitro percutaneous absorption studies were performed using econazole formulations (F2_HPMC dispersion, F4_Lipoderm® Activemax™ Cream) across the ultrasound-treated porcine skin and were compared with the control group (skin samples without ultrasound). Histology and ATR-FTIR studies were performed on treated skin samples. A constant frequency (20 kHz) ultrasound application with 40% amplitude, 0.5 cm distance between ultrasound horn and the skin surface for 2 min was optimized. The permeation of EN was found to be higher from ultrasound-treated skin samples than the control group. Drug permeation from F2_HPMC dispersion was found to be higher as compared to the other formulations and the marketed EN cream. Histological evaluation confirmed that F2_HPMC dispersion showed no signs of toxicity. ATR-FTIR studies revealed a slight increase in the CH2 stretching vibrations (~2920 cm-1 and 2850 cm-1) in ultrasound-treated skin samples as compared with the control. In conclusion, the ultrasound-assisted transdermal delivery of F2_HPMC dispersion could be further studied as a new therapy for Raynaud's phenomenon.


Assuntos
Econazol/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Administração Cutânea , Animais , Antifúngicos/administração & dosagem , Química Farmacêutica/métodos , Permeabilidade , Pele/metabolismo , Absorção Cutânea/fisiologia , Suínos
10.
Acta Biomater ; 101: 507-518, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629894

RESUMO

Treatment of skin infection by dermatophytes is still limited, and the application of conventional topical formulations (ointments, creams, etc.) cause patient discomfort due to repeated administration and low efficacy. This study describes the film-forming system (FFS) hybridized with econazole (ECO)-loaded nanostructured lipid carriers (NLC) for enhanced antifungal activity against dermatophytes. We assumed that the application of NLC could effectively increase the skin permeability of ECO, thereby suppressing the growth of dermatophytes in stratum corneum as well as in epidermis. Meanwhile, ECO-NLC hybrid FFS (ECO-NLC@FFS) could increase the adhesion of ECO-NLC to the skin and prolong the antifungal activity of ECO. First, we optimized ECO-NLC, which shows nanosized particle (199 nm), high encapsulation efficiency (92.5%), and biocompatibility. ECO-NLC@FFS formed a transparent, homogeneous, and hard-to-remove film after topical application. In vitro skin permeation and deposition studies demonstrated that ECO-NLC@FFS showed 1.5-fold higher skin permeation and 3-fold higher ECO deposition in the epidermis layer than a commercial product, which resulted from the nanosized particle and its occlusion effect. And, ex vivo and in vivo antifungal activity studies confirmed that ECO-NLC@FFS improved the skin adhesion of ECO-NLC, thereby allowing ECO to be continuously exposed to the infection sited and reducing the number of applications with a single dose. These results showed that this hybrid system could be a potential for effectively improving the efficacy of antifungal agents and the patient compliance in the treatment of dermatophytes. STATEMENT OF SIGNIFICANCE: Treatment of skin infection by dermatophytes is difficult due to the inconvenience and low efficacy of conventional topical formulations. Here, we demonstrated the potential of a film-forming system (FFS) hybridized with nanostructured lipid carriers (NLC). First, we confirmed that the enhanced skin permeability of drug was improved by NLC. In addition, the hybridization of NLC with FFS improved the skin adhesion of NLC, allowing the drug to exhibit a sustained release profile and prolong antifungal activity. Given the maximized antifungal activity, this hybrid system can be used as a potential pharmaceutical technique to improve patient convenience and achieve complete treatment of skin infection.


Assuntos
Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Portadores de Fármacos/química , Econazol/farmacologia , Lipídeos/química , Nanoestruturas/química , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HaCaT , Humanos , Masculino , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos
11.
Int J Pharm ; 574: 118896, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31765779

RESUMO

Econazole nitrate (ECN) is a weakly basic drug with very low aqueous solubility that hampers its permeation through biological membranes and results in low ECN bioavailability. Formation of drug/cyclodextrin (drug/CD) inclusion complexes is a formulation technology that can be applied to enhance drug solubility in aqueous media. The aim of this study was to determine the effect of CD complexation and pH adjustments on the ECN solubility. The ECN pH-solubility and ECN/CD phase-solubility profiles were determined. The solubility of ECN in aqueous acidic solutions containing α-cyclodextrin (αCD) was relatively high and much higher than in aqueous γ-cyclodextrin (γCD) solutions under same conditions. The complexation efficiency of the ECN/CD complex was relatively low for the unionized drug. Formation of ECN/CD inclusion complex was verified by proton nuclear magnetic resonance spectroscopy. Formation of ECN/CD complexes enhanced the drug stability during autoclaving. γCD complexes self-assembled to form nano- and microparticles whereas αCD complexes had negligible tendency to self-assemble. Formation of CD complex nano- and microparticles was investigated by dynamic light scattering and by drug permeation through semipermeable membranes of different molecular weight cut-off. The largest aggregate fraction was observed for the unionized ECN in aqueous pH 7.5 solution containing high CD concentration, that is 10% (w/v) CD. It was shown that in acidic solutions ECN/αCD can enhance the antifungal activity to filamentous fungi. This was associated with the increased ECN solubility and increase of readily available ECN molecules in aqueous αCD solutions.


Assuntos
Antifúngicos/química , Econazol/química , alfa-Ciclodextrinas/química , gama-Ciclodextrinas/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Difusão Dinâmica da Luz/métodos , Concentração de Íons de Hidrogênio , Nanopartículas/química , Solubilidade/efeitos dos fármacos
12.
Mikrochim Acta ; 187(1): 55, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848716

RESUMO

An electrochromatographic capillary was modified with graphene oxide (GO), and the coating was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, and Fourier transform infrared spectra. By utilizing maltodextrin (MD) as the chiral selector, the basic chiral drugs nefopam (NEF), amlodipine (AML), citalopram hydrobromide (CIT), econazole (ECO), ketoconazole (KET) and cetirizine hydrochloride (CET) can be enantiomerically separated on this CEC. Compared with an uncoated silica capillary, the resolutions are markedly improved (AML: 0.32 → 1.45; ECO: 0.55 → 1.89; KET: 0.88 → 4.77; CET: 0.81 → 2.46; NEF: 1.46 → 2.83; CIT: 1.77 → 4.38). Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results. Graphical abstractSchematic representation of the preparation of graphene oxide-modified capillary (GO@capillary) for enantioseparation of drug enantiomers. The monolayered GO was used as the coating of the GO@capillary. Then the capillary was applied to construct capillary electrochromatography system with maltodextrin for separation of basic chiral drugs.


Assuntos
Grafite/química , Polissacarídeos/química , Anlodipino/química , Anlodipino/isolamento & purificação , Eletrocromatografia Capilar , Cetirizina/química , Cetirizina/isolamento & purificação , Citalopram/química , Citalopram/isolamento & purificação , Econazol/química , Econazol/isolamento & purificação , Cetoconazol/química , Cetoconazol/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Nefopam/química , Nefopam/isolamento & purificação , Tamanho da Partícula , Propriedades de Superfície
13.
Acta Dermatovenerol Croat ; 27(3): 137-141, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542055

RESUMO

Pemphigus vulgaris is an autoimmune disease that mostly affects the mucosa and oral cavity. Candida species can invade the mucosal lesions of these patients and cause diseases. The aim of this study was to identify the fungal agents isolated from mucosal lesions and evaluate antifungal activity profile against the isolates. A total of 25 patients with pemphigus vulgaris with active oral lesions and 25 healthy people serving as a control group were included in this study. Identification of the fungal isolates was performed based on conventional methods and DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. The sequence results were deposited in the NCBI database using the Basic Local Alignment Search Tool. Antifungal activity of fluconazole, itraconazole, ketoconazole, posaconazole, econazole, and amphotericin B against the isolates were evaluated based on the CLSI M-44 A protocol. Oral candidiasis was detected in 20% of the patients. Candida species isolated from oral lesions of patients with pemphigus were identified as Candida albicans 22/25, Candida glabrata 2/25, and Candida dubliniensis 1/25. All of the isolates were sensitive to amphotericin and econazole, 96% to fluconazole and posaconazole, and 92% to ketoconazole and itraconazole. One patient showed a profile resistant to fluconazole, posaconazole, and ketoconazole, simultaneously. Ninety six percent of control group isolates were sensitive to six antifungals. Candida albicans was the most prevalent species isolated from oral lesions of patients with pemphigus vulgaris and the control group. Amphotericin B and econazole were the most effective antifungals against the isolates.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Pênfigo/microbiologia , Adulto , Anfotericina B/farmacologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/patologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Econazol/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Itraconazol/farmacologia , Cetoconazol/farmacologia , Masculino , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Triazóis/farmacologia
14.
Int J Mol Sci ; 20(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357647

RESUMO

Among different Candida species triggering vaginal candidiasis, Candida albicans is the most predominant yeast. It is commonly treated using azole drugs such as Tioconazole (TIO) and Econazole (ECO). However, their low water solubility may affect their therapeutic efficiency. Therefore, the aim of this research was to produce a novel chitosan nanocapsule based delivery system comprising of TIO or ECO and to study their suitability in vaginal application. These systems were characterized by their physicochemical properties, encapsulation efficiency, in vitro release, storage stability, cytotoxicity, and in vitro biological activity. Both nanocapsules loaded with TIO (average hydrodynamic size of 146.8 ± 0.8 nm, zeta potential of +24.7 ± 1.1 mV) or ECO (average hydrodynamic size of 127.1 ± 1.5 nm, zeta potential of +33.0 ± 1.0 mV) showed excellent association efficiency (99% for TIO and 87% for ECO). The analysis of size, polydispersity index, and zeta potential of the systems at 4, 25, and 37 °C (over a period of two months) showed the stability of the systems. Finally, the developed nanosystems presented fungicidal activity against C. albicans at non-toxic concentrations (studied on model human skin cells). The results obtained from this study are the first step in the development of a pharmaceutical dosage form suitable for the treatment of vaginal candidiasis.


Assuntos
Antifúngicos/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Fenômenos Químicos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Econazol/administração & dosagem , Econazol/química , Imidazóis/administração & dosagem , Imidazóis/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nanocápsulas/química , Nanopartículas/ultraestrutura
15.
FASEB J ; 33(8): 9526-9539, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121099

RESUMO

The classic concept that GPCRs function as monomers has been challenged by the emerging evidence of GPCR dimerization and oligomerization. Rhodopsin (Rh) is the only GPCR whose native oligomeric arrangement was revealed by atomic force microscopy demonstrating that Rh exists as a dimer. However, the role of Rh dimerization in retinal physiology is currently unknown. In this study, we identified econazole and sulconazole, two small molecules that disrupt Rh dimer contacts, by implementing a cell-based high-throughput screening assay. Racemic mixtures of identified lead compounds were separated and tested for their stereospecific binding to Rh using UV-visible spectroscopy and intrinsic fluorescence of tryptophan (Trp) 265 after illumination. By following the changes in UV-visible spectra and Trp265 fluorescence in vitro, we found that binding of R-econazole modulates the formation of Meta III and quenches the intrinsic fluorescence of Trp265. In addition, electrophysiological ex vivo recording revealed that R-econazole slows photoresponse kinetics, whereas S-econazole decreased the sensitivity of rods without effecting the kinetics. Thus, this study contributes new methodology to identify compounds that disrupt the dimerization of GPCRs in general and validates the first active compounds that disrupt the Rh dimer specifically.-Getter, T., Gulati, S., Zimmerman, R., Chen, Y., Vinberg, F., Palczewski, K. Stereospecific modulation of dimeric rhodopsin.


Assuntos
Rodopsina/química , Rodopsina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Econazol/farmacologia , Eletrofisiologia , Humanos , Imidazóis/farmacologia , Immunoblotting , Cinética , Multimerização Proteica/efeitos dos fármacos
16.
J Hazard Mater ; 374: 203-210, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31003121

RESUMO

Stability and toxicity studies for duloxetine and econazole were achieved using individual solutions and their mixtures. Stability of drugs racemates and enantiomers was investigated under abiotic and biotic conditions. Toxicity was evaluated for the first time on Spirodela polyrhiza. EC50 values were calculated for each individual drug and for their binary mixture. Real (not nominal) concentrations determined by Capillary Electrophoresis were employed in the calculations of toxicity parameters. The use of a 25 mM phosphate buffer (pH 3.0) with 1.5% S-ß-CD as chiral selector at a temperature of 30 °C and a separation voltage of -20 kV enabled the simultaneous enantiomeric separation of duloxetine and econazole in 7.5 min with enantiomeric resolutions of 7.9 and 6.5, respectively. For individual solutions, decay percentages under abiotic conditions were higher for duloxetine (80%) than for econazole (60%), while in presence of Spirodela polyrhiza they increased for duloxetine but not for econazole. Econazole showed the highest decay percentages under abiotic or biotic conditions (100%) in binary mixtures. EC50 values for duloxetine and econazole enabled to include both drugs within the group of very toxic compounds although econazole showed a higher toxicity than duloxetine and the binary mixture.


Assuntos
Araceae/efeitos dos fármacos , Cloridrato de Duloxetina/toxicidade , Econazol/toxicidade , Tampões (Química) , Clorofila/química , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Eletroforese Capilar , Estereoisomerismo , Temperatura , Testes de Toxicidade
17.
Sci Total Environ ; 670: 770-778, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30921710

RESUMO

Enantiomer stability was investigated in this work for the first time for duloxetine and econazole in individual solutions and their mixtures under the standardized ecotoxicity test experimental conditions for Daphnia magna and abiotic conditions. Real (and not nominal) enantiomer concentrations were employed for calculations since their determination was achieved by Capillary Electrophoresis. Relevant differences were found in stability profiles for both drugs in any case. Toxicity was evaluated for the first time in this work for mixtures of duloxetine and econazole on Daphnia magna. Dose-effect parameters were calculated at different exposure times (24, 48, and 72 h) showing a significant inhibition of daphnids mobility when increasing the incubation time. Combination index values enabled to obtain the type and level of interaction of drugs with the organism. A strong synergism was observed at 48 h exposure time and any effect level, which demonstrated the high toxicity of the drug mixture compared with the individual drug solutions. These results were corroborated when evaluating the oxidative stress using fluorescence images.


Assuntos
Cloridrato de Duloxetina/toxicidade , Econazol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia , Eletroforese Capilar , Estresse Oxidativo , Estereoisomerismo , Testes de Toxicidade Aguda
18.
Pharm Dev Technol ; 24(6): 689-699, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30712434

RESUMO

The purpose of this work was to design and characterize a topical formulation of econazole nitrate (EN) with potential for treating Raynaud's phenomenon (RP). Four topical dosage forms (F1_topical solution, F2_HPMC or hydroxypropyl methylcellulose dispersion, F3_VersaBase® cream, and F4_Lipoderm® Activemax™ Cream) containing 3% w/w EN were prepared and characterized for drug content, pH, viscosity, spreadability, drug crystallinity, stability, and in vitro permeation using Franz cells across pig ear skin, and results were compared to the 1% marketed EN cream. All four formulations had acceptable physical and visual characteristics required for topical application, with 3% w/w EN. The order of amount of drug permeated from highest to lowest was F2 (10.27%) > F4 (2.47%) > F1 (2.28%) > F3 (1.47%) > marketed formulation (0.22%). Formulation F2 showed better penetration of the drug into the stratum corneum, epidermis, and dermis layers. The drug concentration in the stratum corneum and epidermis was approximately 10-20 times higher with F2 compared to the marketed formulation. All formulations were found to be stable for up to 6 months. All four EN formulations were found to be better than the 1% marketed cream. Formulation F2_HPMC dispersion could be further explored as a treatment option for RP.


Assuntos
Inibidores de 14-alfa Desmetilase/administração & dosagem , Antifúngicos/administração & dosagem , Econazol/administração & dosagem , Veículos Farmacêuticos/química , Doença de Raynaud/tratamento farmacológico , Inibidores de 14-alfa Desmetilase/farmacocinética , Administração Tópica , Animais , Antifúngicos/farmacocinética , Cristalização , Composição de Medicamentos/métodos , Econazol/farmacocinética , Humanos , Derivados da Hipromelose/química , Doença de Raynaud/metabolismo , Absorção Cutânea , Suínos
19.
Toxicol Sci ; 169(1): 209-223, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698772

RESUMO

Tebuconazole and Econazole are triazole and imidazole fungicides currently used worldwide. Although their reproductive toxicity in mammals has been described, their effect on male reproductive systems has been poorly investigated. As humans may be exposed to different azole compounds simultaneously, the combinational in vitro toxicity of Tebuconazole and Econazole (MIX) in mouse Sertoli TM4 cells was investigated. This study demonstrates that Tebuconazole (40 µM) and Econazole (20 µM) act synergistically in mediating decrease of mitochondrial membrane potential (ΔΨm) and changes in mitochondrial morphology. These events were associated with ATP depletion, cell cycle arrest, and sequential activation of autophagy and apoptosis. Remarkable differences on other parameters such as AMP/ATP ratio and adenylate energy charge were observed. Pharmacological inhibition of autophagy by bafilomycin A1 leads to enhanced MIX-induced apoptosis suggesting an adaptive cytoprotective function for MIX-modulated autophagy. Finally, a possible role of AMPK/ULK1 axis in mediating adaptive signalling cascades in response to energy stress was hypothesized. Consistently, ULK1 Ser 555 phosphorylation occurred in response to AMPK (Thr 172) activation. In conclusion, Tebuconazole and Econazole combination, at concentrations relevant for dermal and clinical exposure, induces a severe mitochondrial stress in SCs. Consequently, a prolonged exposure may affect the ability of the cells to re-establish homeostasis and trigger apoptosis.


Assuntos
Antifúngicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Econazol/toxicidade , Metabolismo Energético/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Mitocôndrias/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Triazóis/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...