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1.
J Chromatogr Sci ; 57(10): 867-873, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31602483

RESUMO

Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 µm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 µg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 µg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fluoroquinolonas/análise , Miconazol/análise , Furoato de Mometasona/análise , Quinolizinas/análise , Cromatografia de Fase Reversa , Fluoroquinolonas/sangue , Fluoroquinolonas/química , Humanos , Limite de Detecção , Modelos Lineares , Miconazol/sangue , Miconazol/química , Furoato de Mometasona/sangue , Furoato de Mometasona/química , Quinolizinas/sangue , Quinolizinas/química , Reprodutibilidade dos Testes
2.
Pol J Microbiol ; 68(4): 477-491, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880892

RESUMO

This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 - 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 ­ 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Farmacorresistência Bacteriana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , beta-Lactamas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriólise/efeitos dos fármacos , Cloxacilina/farmacologia , Quimioterapia Combinada , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Miconazol/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/citologia , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Tioridazina/farmacologia
3.
AAPS PharmSciTech ; 20(7): 297, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444661

RESUMO

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Química Farmacêutica/métodos , Ácido Hialurônico/administração & dosagem , Miconazol/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Animais , Antifúngicos/síntese química , Antifúngicos/farmacocinética , Candidíase Bucal/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/síntese química , Emulsões/farmacocinética , Ácido Hialurônico/síntese química , Ácido Hialurônico/farmacocinética , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/farmacocinética , Miconazol/síntese química , Miconazol/farmacocinética , Nanocápsulas/química , Ovinos
4.
EMBO Mol Med ; 11(8): e10291, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31318166

RESUMO

Optic nerve atrophy represents the most common form of hereditary optic neuropathies leading to vision impairment. The recently described Bosch-Boonstra-Schaaf optic atrophy (BBSOA) syndrome denotes an autosomal dominant genetic form of neuropathy caused by mutations or deletions in the NR2F1 gene. Herein, we describe a mouse model recapitulating key features of BBSOA patients-optic nerve atrophy, optic disc anomalies, and visual deficits-thus representing the only available mouse model for this syndrome. Notably, Nr2f1-deficient optic nerves develop an imbalance between oligodendrocytes and astrocytes leading to postnatal hypomyelination and astrogliosis. Adult heterozygous mice display a slower optic axonal conduction velocity from the retina to high-order visual centers together with associative visual learning deficits. Importantly, some of these clinical features, such the optic nerve hypomyelination, could be rescued by chemical drug treatment in early postnatal life. Overall, our data shed new insights into the cellular mechanisms of optic nerve atrophy in BBSOA patients and open a promising avenue for future therapeutic approaches.


Assuntos
Fator I de Transcrição COUP/genética , Haploinsuficiência , Fibras Nervosas Mielinizadas/ultraestrutura , Atrofia Óptica Autossômica Dominante/genética , Nervo Óptico/ultraestrutura , Animais , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Comportamento Animal , Fator I de Transcrição COUP/deficiência , Modelos Animais de Doenças , Predisposição Genética para Doença , Heterozigoto , Humanos , Aprendizagem , Camundongos Knockout , Miconazol/farmacologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/metabolismo , Condução Nervosa , Oligodendroglia/metabolismo , Oligodendroglia/ultraestrutura , Atrofia Óptica Autossômica Dominante/tratamento farmacológico , Atrofia Óptica Autossômica Dominante/metabolismo , Atrofia Óptica Autossômica Dominante/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/metabolismo , Percepção Visual
5.
J Eur Acad Dermatol Venereol ; 33(10): 1863-1873, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31287594

RESUMO

Cutaneous candidiasis is a common skin disease, and several treatments have been investigated within the last fifty years. Yet, systematic reviews are lacking, and evidence-based topical and systemic treatment strategies remain unclear. Thus, the aim of this review was to summarize efficacy and adverse effects of topical and oral therapies for cutaneous candidiasis in all age groups. Two individual researchers searched PubMed and EMBASE for 'cutaneous candidiasis' and 'cutaneous candidiasis treatment', 'intertrigo', 'diaper dermatitis' and 'cheilitis'. Searches were limited to 'English language', 'clinical trials' and 'human subjects', and prospective clinical trials published in abstracts or articles were included. In total, 149 studies were identified, of which 44 were eligible, comprising 41 studies of 19 topical therapies and four studies of three systemic therapies for cutaneous candidiasis. Topical therapies were investigated in infants, children, adolescents, adults and elderly, while studies of systemic therapies were limited to adolescents and adults. Clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated similar efficacy with complete cure rates of 73%-100%. Single-drug therapy was as effective as combinations of antifungal, antibacterial and topical corticosteroid. Four studies investigated systemic therapy, and oral fluconazole demonstrated similar efficacy to oral ketoconazole and topical clotrimazole. Limitations to this review were mainly that heterogeneity of studies hindered meta-analyses. In conclusions, clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated equal good efficacy and mild adverse effects similar to combinations of antifungal, antibacterial and topical corticosteroids. Oral fluconazole was as effective as topical clotrimazole and is the only commercially available evidence-based option for systemic treatment of cutaneous candidiasis.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Cutânea/tratamento farmacológico , Clotrimazol/uso terapêutico , Fluconazol/uso terapêutico , Miconazol/uso terapêutico , Nistatina/uso terapêutico , Administração Oral , Administração Tópica , Antifúngicos/administração & dosagem , Clotrimazol/administração & dosagem , Quimioterapia Combinada , Medicina Baseada em Evidências , Fluconazol/administração & dosagem , Humanos , Cetoconazol/uso terapêutico , Miconazol/administração & dosagem , Nistatina/administração & dosagem
6.
Pharmazie ; 74(5): 290-294, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109399

RESUMO

In recent years, "drug repurposing" has become an important approach and focus of studies on anti-tumor drug research and development (R&D). As one of the first-generation broad-spectrum imidazole anti-fungal drugs, miconazole (MCZ) exhibits anti-tumor effects in addition to its anti-fungal effect. However, no report has focused on examining the effect of MCZ on the proliferation and cell-death of human breast cancer MDA-MB-231 cells. MCZ significantly inhibited the proliferation of MDA-MB-231 cells in a concentration- and time-dependent manner. We also observed that MCZ induced both apoptosis and necroptosis in MDA-MB-231 cells. Transmission electron microscopy showed submicroscopic structures in these cells, which correspond to necrotic features, in addition to the characteristic features of apoptosis. Pretreatment of cells with z-VAD-fmk, an apoptosis inhibitor or Nec-1, a necroptosis inhibitor, significantly increased their viability compared with MCZ treatment. The initial mechanism of MCZ-mediated cell death in human breast cancer MDA-MB-231 cells involves an increase in the Bax/Bcl-2 ratio, downregulation of apoptosis induced by Akt and p-Akt-473, a simultaneous upregulation of the receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) protein expression, and ROS production to induce necroptosis. Our results suggest that MCZ may be a potential lead compound for the development of anti-breast cancer drugs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Miconazol/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Necroptose/efeitos dos fármacos , Necrose/tratamento farmacológico , Proteína Serina-Treonina Quinases de Interação com Receptores
7.
Hautarzt ; 70(11): 888-896, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31098692

RESUMO

A 6 month-old-female infant from Bahrain visiting Germany with her family for a holiday was seen by us for extensive dermatophytosis of the back, buttocks, chest and groins. Topical treatment by terbinafine for over 2 months was not successful. Other family members including adults and children were treated in Bahrain with topical antifungals and oral voriconazole which was not helpful. Mycological examination performed in Germany revealed the detection of the zoophilic dermatophyte Trichophyton (T.) mentagrophytes. The newly described genotype VIII within the species T. mentagrophytes was identified by sequencing of the "internal transcribed spacer" (ITS) region of the fungal rDNA. This genotype of T. mentagrophytes is the main causative agent of the current epidemic of chronic recalcitrant dermatophytoses in India. Transmission of this Indian genotype of T. mentagrophytes to other countries due to globalization is a serious issue to be considered. Moreover, a significant percentage of these Indian T. mentagrophytes strains are resistant to terbinafine both in vitro and by the way of genetic point mutations in the squalene epoxidase (SQLE) gene. Some are also found to be partially resistant against itraconazole and voriconazole. The point mutation TTC/TTA was found by SQLE mutation analysis in this particular T. mentagrophyte isolate from Bahrain. This point mutation is closely associated with F397L amino acid substitution of the enzyme indicative of in vitro resistance of the dermatophyte against terbinafine. The girl was successfully treated by topical miconazole and later by ciclopirox olamine. This is the first report on an infection due to a terbinafine-resistant T. mentagrophytes strain of the ITS genotype VIII from India in Germany.


Assuntos
Antifúngicos/farmacologia , Ciclopirox/uso terapêutico , Miconazol/uso terapêutico , Terbinafina/farmacologia , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha/tratamento farmacológico , Trichophyton/genética , Trichophyton/isolamento & purificação , Adulto , Antifúngicos/uso terapêutico , Barein , Feminino , Genótipo , Alemanha , Humanos , Lactente , RNA Fúngico , Análise de Sequência de RNA , Terbinafina/uso terapêutico , Tinha/diagnóstico , Tinha do Couro Cabeludo/diagnóstico , Trichophyton/classificação
8.
J Appl Microbiol ; 127(1): 68-77, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31013388

RESUMO

AIMS: Candida albicans biofilms are commonly associated with severe oral infections. We previously discovered that a crude extract from the Solidago virgaurea plant (SV extract) was a potent inhibitor of C. albicans biofilm formation. Here, we further investigate the mechanisms underlying C. albicans biofilm inhibition by the SV extract. METHODS AND RESULTS: The SV extract was shown to inhibit laboratory and clinical C. albicans isolates adherence and hyphal transition on inert support and epithelial human cells, without affecting viability and growth of planktonic yeasts. Interestingly, RT-PCR-based experiments demonstrated that some key genes involved in adhesion and hyphal morphological switch (e.g. Hwp1p, Ece1p, Als3p) were strongly down-regulated by the SV extract. Moreover, antimicrobial synergy testing (checkerboard assay) demonstrated that antifungal effects of miconazole, nystatin or a common antiseptic mouthwash were synergistically improved when used in combination with the SV extract. CONCLUSIONS: The SV extract prevents C. albicans biofilm formation through direct inhibition of key adherence and hyphae-associated genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilm is considered as a key virulence factor of C. albicans infection. Our discovery of an inhibitor specifically acting on genes involved in biofilm formation paves the way for the future development of a new class of antifungal product.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Extratos Vegetais/farmacologia , Solidago/química , Antifúngicos/farmacologia , Células Cultivadas , Sinergismo Farmacológico , Expressão Gênica/efeitos dos fármacos , Humanos , Hifas/efeitos dos fármacos , Miconazol/farmacologia , Nistatina/farmacologia , Extratos Vegetais/química
10.
Vet Dermatol ; 30(3): 183-e57, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30887651

RESUMO

BACKGROUND: Topical therapy alone can be effective in the treatment of canine pyoderma. Topical products are commercially available as shampoos, sprays, wipes and mousses. To date, no studies have evaluated the efficacy of commercially available mousse products in the treatment of canine pyoderma. OBJECTIVE: To determine the residual antibacterial activity of canine hairs treated with mousse products containing different active ingredients. ANIMALS: Fifteen client-owned dogs with no history of dermatological disease. METHODS AND MATERIALS: Dogs were treated once with five mousse products [(i) 2% chlorhexidine and 1% ketoconazole, (ii) 2% chlorhexidine and 2% miconazole, (iii) 3% chlorhexidine and 0.5% climbazole, (iv) 2% salicylic acid 10% ethyl lactate and (v) phytosphingosine HCl 0.05%; control]. Hair samples were collected from each treatment area before application, one hour after application and on days 2, 4, 7, 10 and 14 post-treatment. Collected hairs were weighed and plated on Mueller-Hinton agar plates streaked with a Staphylococcus pseudintermedius isolate showing no antimicrobial resistance. Plates were incubated for 24 h and bacterial growth inhibition zones around the hairs were measured. RESULTS: Mousses 1, 2 and 3 created significant inhibition zones up to Day 10 when compared to pre-treatment samples. On Day 14, only mousse 3 produced a significant zone of inhibition when compared to the pre-treatment sample. Mousses 4 and 5 showed no statistical difference between any of the samples. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that three of the mousse products had residual activity in inhibiting S. pseudintermedius growth in vitro for at least 10 days.


Assuntos
Antibacterianos/análise , Resíduos de Drogas/análise , Preparações para Cabelo/química , Pioderma/veterinária , Infecções Cutâneas Estafilocócicas/veterinária , Staphylococcus/efeitos dos fármacos , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Clorexidina/administração & dosagem , Doenças do Cão/tratamento farmacológico , Cães , Cabelo , Cetoconazol/administração & dosagem , Miconazol/administração & dosagem , Testes de Sensibilidade Microbiana , Animais de Estimação , Pioderma/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico
11.
Med Oral Patol Oral Cir Bucal ; 24(2): e172-e180, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818309

RESUMO

BACKGROUND: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. MATERIAL AND METHODS: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. RESULTS: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. CONCLUSIONS: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Bucal/tratamento farmacológico , Administração Intravenosa , Administração Oral , Administração Tópica , Anfotericina B/uso terapêutico , Anidulafungina/uso terapêutico , Azóis/uso terapêutico , Caspofungina/uso terapêutico , Clotrimazol/uso terapêutico , Bases de Dados Factuais , Interações Medicamentosas , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Humanos , Miconazol/uso terapêutico , Nitrilos/uso terapêutico , Nistatina/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico
12.
Med. oral patol. oral cir. bucal (Internet) ; 24(2): e172-e180, mar. 2019.
Artigo em Inglês | IBECS | ID: ibc-180640

RESUMO

Background: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. Material and Methods: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. Results: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. Conclusions: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B


No disponible


Assuntos
Humanos , Candida/isolamento & purificação , Candidíase Bucal/tratamento farmacológico , Antifúngicos/uso terapêutico , Miconazol/uso terapêutico , Nistatina/uso terapêutico , Anfotericina B/uso terapêutico , Fluconazol/uso terapêutico , Equinocandinas/uso terapêutico
13.
Chem Pharm Bull (Tokyo) ; 67(2): 106-111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713269

RESUMO

The purpose of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres (MS) loaded with itraconazole (ITCZ) or miconazole (MCZ) under different evaporation temperatures (25 or 40°C) using an oil-in-water emulsion solvent evaporation method in order to evaluate the initial burst release of drug. Loading efficiencies were comparatively good and the diameters of prepared drug-loaded PLGA MS were around 20 µm in all formulations. The release rates of ITCZ-PLGA MS prepared at 40°C showed a significantly restricted release profile compared with the corresponding ITCZ-PLGA MS prepared at 25°C. This difference in release rate of ITCZ was thought to be caused by the self-healing effect of PLGA, as the glass transition temperature of PLGA is around 40°C. With respect to the MCZ-PLGA MS, the initial burst release was similar in formulations prepared at both 25 and 40°C. Scanning electron microscope results suggested that the initial burst release was due to the localization of MCZ on the surface of MCZ-PLGA MS at higher concentrations. Differential scanning calorimetry measurements suggested complete amorphization of MCZ in MCZ-PLGA MS, whereas crystalline ITCZ was detected in the ITCZ-PLGA MS. This complete amorphization of MCZ is considered to be one of the reasons for the initial burst release.


Assuntos
Portadores de Fármacos/química , Itraconazol , Miconazol , Microesferas , Poliglactina 910 , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Itraconazol/química , Miconazol/química
14.
Med Mal Infect ; 49(3): 194-201, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30792037

RESUMO

OBJECTIVE: An empirical treatment of infectious vaginitis is justified because of its multiple etiologies, the frequent uncertainty of clinical diagnosis and limits of microbiological analysis. Our aim was to comparatively investigate nystatin-neomycin-polymyxin B combination (NNP, Polygynax®) and miconazole. PATIENTS AND METHODS: In this European multicenter, double-blind PRISM trial, participating women presenting with infectious vaginitis were randomized to receive one vaginal capsule containing either NNP for 12 days or miconazole for 3 days followed by 9 days of placebo. RESULTS: The clinical success rate was higher in the NNP group (n=302) than the miconazole group (n=309), with a difference between groups close to statistical significance (91.1% vs. 86.7%, P=0.0906). The risk of treatment failure was 36% lower in the NNP group (odds ratio, 0.64; 95% confidence interval, 0.38-1.07). Vaginal burning on Day 2 and vaginal discharge on Day 4 were significantly less intense in the NNP group than in the miconazole group (39.1 vs. 42.3, P=0.031 and 34.6 vs. 37.6, P=0.031, respectively). Adverse drug reactions were reported by 1.2% and 2.1% of patients in the NNP and miconazole group respectively, with the ratio of adverse drug reactions relative to total adverse events significantly higher in the miconazole group (20.3% vs. 6.9%, P=0.022). CONCLUSION: The widespread use of NNP for several decades and its good efficacy and safety profile, as well as the frequent diagnostic uncertainties due to the various pathogens sustain the initiation of this broad-spectrum empirical treatment in infectious vaginitis.


Assuntos
Arsenicais/administração & dosagem , Miconazol/administração & dosagem , Neomicina/administração & dosagem , Nistatina/administração & dosagem , Polimixinas/administração & dosagem , Vaginite/tratamento farmacológico , Adolescente , Adulto , Arsenicais/efeitos adversos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/epidemiologia , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Miconazol/efeitos adversos , Pessoa de Meia-Idade , Neomicina/efeitos adversos , Nistatina/efeitos adversos , Polimixinas/efeitos adversos , Resultado do Tratamento , Vaginite/epidemiologia , Vaginite/microbiologia , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/epidemiologia , Adulto Jovem
17.
Colloids Surf B Biointerfaces ; 174: 409-415, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481701

RESUMO

OBJECTIVES: In this study, polymeric nanoparticles based on chitosan incorporating the antifungal miconazole nitrate were fabricated and testedin vivo using murine vulvovaginal candidiasis. METHODS: Nanoparticles prepared by the ionotropic gelation method presented 200 to 300 nm diameter and polydispersity indexes ranging from 0.2 to 0.4. The nanoparticles were prepared to incorporate 63.9 mg/mL of miconazole nitrate to be testedin vivo. Murine vulvovaginal candidiasis was standardized using estradiol valerate before the animals were challenged by Candida albicans. RESULTS: The treatment using chitosan nanoparticles within miconazole nitrate presented the same therapeutic efficacy as miconazole nitrate in a commercial cream formulation, however using the antifungal content about seven-fold lower. This increase in the miconazole nitrate's therapeutic efficacy is may be due to the down-regulation of interleukin 10 (IL-10) expression. CONCLUSIONS: Our data represent a proof of concept that can be exploited to achieve an alternative and promising therapy for the treatment of vulvovaginal candidiasis.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Quitosana/química , Miconazol/farmacologia , Nanopartículas/administração & dosagem , Administração Intravaginal , Animais , Antifúngicos/química , Candidíase Vulvovaginal/microbiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Miconazol/química , Nanopartículas/química
18.
Med Mycol ; 57(1): 52-62, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361177

RESUMO

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.


Assuntos
Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Farneseno Álcool , Miconazol , Nanopartículas/química , Animais , Antifúngicos/síntese química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Células 3T3 BALB , Candida albicans/crescimento & desenvolvimento , Candidíase Vulvovaginal/patologia , Cápsulas , Quitosana/química , Modelos Animais de Doenças , Farneseno Álcool/química , Farneseno Álcool/farmacologia , Farneseno Álcool/uso terapêutico , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Miconazol/química , Miconazol/farmacologia , Miconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/uso terapêutico
19.
Mycopathologia ; 184(1): 187-192, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29761326

RESUMO

Superficial mycoses are commonly reported in captive pinnipeds, usually maintained in wet and warm environments, favorable to fungal growth. Most superficial mycoses in pinnipeds have been described as difficult to treat; however, the majority of the reports come from past decades. Cutaneous lesions associated with opportunistic Fusarium sp. infections have been previously recognized in this taxon. We described the clinical signs, associated lesions and diagnosis (thermography, imprint cytology, histopathology, culture, electron microscopy, PCR) of a fusariosis case by Fusarium sp. in the nails and skin of an adult male captive South American sea lion (Otaria flavescens) recently transferred from another zoological institution, and its successful long-term treatment with Ketoconazole PO (60 days) and Miconazole solution spray TO, followed by Itraconazole PO (30 days). Herein we provide a successful approach to the diagnosis and treatment of fusariosis.


Assuntos
Fusariose/veterinária , Fusarium/isolamento & purificação , Leões-Marinhos , Animais , Antifúngicos/administração & dosagem , Cães , Fusariose/diagnóstico , Fusariose/microbiologia , Histocitoquímica , Itraconazol/administração & dosagem , Cetoconazol/administração & dosagem , Masculino , Miconazol/administração & dosagem , Técnicas Microbiológicas , Técnicas de Diagnóstico Molecular , Pele/microbiologia , Pele/patologia , América do Sul , Resultado do Tratamento
20.
Med Mycol ; 57(3): 324-327, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29924372

RESUMO

The yeast Malassezia pachydermatis is a common commensal and occasional opportunistic pathogen of theskin microbiota of animals and humans. In this study, the susceptibility of M. pachydermatis isolates to fluconazole (FLC), itraconazole (ITZ), ketoconazole (KTZ), clotrimazole (CLZ), and miconazole (MCZ) alone and in combination with terbinafine (TRB), nystatin (NYS), and caspofungin (CSP) was evaluated in vitro based on the M27-A3 technique and the checkerboard microdilution method using Sabouraud dextrose broth with 1% tween 80 (SDB). Based on the mean FICI values, the main synergies observed were combinations of ITZ+CSP and CLZ+CSP (55.17%). The most significant combinations deserve in vivo evaluations because might provide effective alternative treatments against M. pachydermatis due to their synergistic interactions.


Assuntos
Antifúngicos/farmacologia , Malassezia/efeitos dos fármacos , Combinação de Medicamentos , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Itraconazol/farmacologia , Miconazol/farmacologia , Testes de Sensibilidade Microbiana
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