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Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to its poor bioavailability we further investigated whether nanoparticles (NPs) made of zein protein may constitute a safe and effective choice to incorporate MF. Thus, in this work, we loaded MF into zein NPs aiming to evaluate possible advantages that could result from oral delivery and extend the range of MF application such as inflammatory gut diseases. MF-loaded zein NPs presented an average size in the range of 100 and 135 nm, narrow size distribution (polydispersity index < 0.300), zeta potential of around + 10 mV and association efficiency of MF over 70%. Transmission electron microscopy imaging revealed that NPs had a round shape and presented a smooth surface. The zein NPs showed low MF release in a buffer that mimics the gastric condition (pH = 1.2) and slower and controlled MF release in the intestinal condition (pH = 6.8). The short and intermediate safety of zein NPs was confirmed assessing the incubation against Caco-2 and HT29-MTX intestinal cells up to 24 h. Permeability studies of MF across Caco-2/HT29-MTX co-culture monolayer evidenced that zein NPs modulated MF transport across cell monolayer resulting in a stronger and prolonged interaction with mucus, potentially extending the time of absorption and overall local and systemic bioavailability. Overall, zein NPs showed to be suitable to carry MF to the intestine and future studies can be developed to investigate the use of MF-loaded zein NPs to treat intestinal inflammatory diseases.

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Abstract Objectives: Nigella sativa oil is known antiallergic and immunomodulatory effects. We aimed to compare this oil with mometasone furoate, a topical steroid, on a rat model in the prevention of allergic rhinitis symptoms. Methods: A total of 28 two-to-four-month-old Wistar Hannover rats weighing 250-350 g were randomly divided into four groups of seven, which included control, allergic rhinitis, mometasone furoate, and Nigella sativa oil groups. Loss of cilia, an increase of goblet cells, vascular proliferation, inflammatory cell count, eosinophil infiltration, and the degree of hypertrophy in chondrocytes were assessed by light microscopy. Results: The frequency of nasal scratching in the Nigella sativa oil group was found to be significantly lower compared with the allergic rhinitis group (p < 0.05). Typical inflammatory changes seen in allergic rhinitis were not detected in the Nigella sativa oil group. No inflammation was observed in 85.7% of both the healthy control group and the Nigella sativa oil group. In addition, no inflammation was observed in 71.4% of the mometasone furoate group, and this difference was found to be significant compared with the control group (p < 0.05). In addition, eosinophil infiltration, cilia loss, chondrocyte hypertrophy, vascular proliferation, and goblet cell increase were found to be significantly decreased in the mometazone furoate and Nigella sativa oil groups compared to the allergic rhinitis group (p < 0.05). Conclusion: According to the findings obtained from this study, we found anti-inflammatory and anti-allergic effects of Nigella sativa oil as equally effective as mometasone furoate in the treatment of experimentaly generated allergic rhinitis. Level of evidence: IV.

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OBJECTIVES: Nigella sativa oil is known antiallergic and immunomodulatory effects. We aimed to compare this oil with mometasone furoate, a topical steroid, on a rat model in the prevention of allergic rhinitis symptoms. METHODS: A total of 28 two-to-four-month-old Wistar Hannover rats weighing 250-350 g were randomly divided into four groups of seven, which included control, allergic rhinitis, mometasone furoate, and Nigella sativa oil groups. Loss of cilia, an increase of goblet cells, vascular proliferation, inflammatory cell count, eosinophil infiltration, and the degree of hypertrophy in chondrocytes were assessed by light microscopy. RESULTS: The frequency of nasal scratching in the Nigella sativa oil group was found to be significantly lower compared with the allergic rhinitis group (p < 0.05). Typical inflammatory changes seen in allergic rhinitis were not detected in the Nigella sativa oil group. No inflammation was observed in 85.7% of both the healthy control group and the Nigella sativa oil group. In addition, no inflammation was observed in 71.4% of the mometasone furoate group, and this difference was found to be significant compared with the control group (p < 0.05). In addition, eosinophil infiltration, cilia loss, chondrocyte hypertrophy, vascular proliferation, and goblet cell increase were found to be significantly decreased in the mometazone furoate and Nigella sativa oil groups compared to the allergic rhinitis group (p < 0.05). CONCLUSION: According to the findings obtained from this study, we found anti-inflammatory and anti-allergic effects of Nigella sativa oil as equally effective as mometasone furoate in the treatment of experimentaly generated allergic rhinitis. LEVEL OF EVIDENCE: IV.

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Biodegradable polymeric nanofibers containing mometasone furoate can be a new approach to drug delivery to treat chronic rhinosinusitis, providing controlled steroid delivery to the sinonasal mucosa. This study aimed to develop biodegradable polymeric nanofibers and explore the safety of these fibers in an in vivo rabbit model. The nanofibers' development has been optimized using the Response Surface Methodology (RSM) obtained with Design of Experiments (DoE) with the best conditions related to the polymer concentration and proportion of solvents used in the electrospinning process. The nanofibers were prepared, operating as a determinant factor, the nanofiber formation and its diameter evaluated by Scanning Electron Microscopy (SEM). The ideal system obtained was assessed by SEM, thermogravimetric analysis (TGA), X-ray diffraction (XRD), differential scanning calorimetry (DSC), assay, and drug delivery by UHLPC validated method. The results showed that the drug is dispersed in the polymeric matrix, is stable, and showed sustained release kinetics in a bio-relevant nasal environment (Higuchi model kinetics). In vivo tests, the level of inflammation at the animals' mucosa which received the nanofiber with the mometasone furoate was lower than those that received the nanofibers without the drug (α = 0.05). Histopathology analysis showed that the polymeric nanofibers containing mometasone are safe when topically applied on the sinonasal mucosa, opening a new horizon in chronic rhinosinusitis treatment.

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Cleaning validation is the documented evidence that shows the effectiveness of cleaning procedures for the removal of product residues and other contaminants. The cleaning procedures must be validated and methods to determine trace amounts of drugs have to be considered with special attention. An ultra-high-performance liquid chromatography-ultraviolet (UHPLC-UV) method for the determination of mometasone furoate residues on stainless-steel surfaces was developed and validated in order to control a cleaning procedure. The chromatography separation was achieved on a Waters Acquity UPLC HSS T3 column (50 × 2.1 mm, 1.8 µm) at 40°C using acetonitrile and water (1:1, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The injection volume was 2 µL, and the detection was performed at 254 nm. The swab and rinse procedures were optimized in order to obtain a recovery higher than 90% of mometasone furoate from stainless-steel surfaces, using ethanol as the extraction solvent. The method was validated in the range of 0.2-2.6 µg/mL and showed appropriate selectivity, limit of detection and quantification, linearity, precision, accuracy, and robustness. This method was found to be simple, fast, and sensitive for determination of mometasone furoate residues and, therefore, can be used for cleaning validation analysis.

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INTRODUCTION: Prevalence of diseases associated with ageing is rising; among these are the rhinologic problems. Chronic rhinitis appears as one of the most common worrisome nasal disorders in this age group. At the same time, the allergic form diminishes because of the immunosenescence. OBJECTIVE: This study aimed to evaluate the effect of a corticosteroid nasal spray (mometasone furoate) over nasal patency and the severity of rhinitis and its impacts on quality of life as compared with the saline nasal spray. METHODS: This open label-trial randomized subjects ≥60y with chronic rhinitis (allergic and nonallergic rhinitis) with mometasone spray 100mcg/d and isotonic saline nasal spray or saline alone for two weeks. The primary endpoint was the improvement in nasal patency evaluated by the peak nasal inspiratory flow (PNIF). Secondary outcomes included the severity of symptoms and the quality of life assessed by a visual analogic scale (VAS) and the sinonasal outcome test (SNOT-22), respectively. RESULTS: Forty patients underwent randomization, in equal number in each group of treatment, either with allergic (AR) and nonallergic rhinitis (NAR). At week 2, the mean PNIF score was 79.5 in the corticosteroid (CE) plus saline group and 82.0 in the saline group (p = 0.37). Also, SNOT-22 and VAS were not improved with the addition of mometasone furoate. CONCLUSIONS: Treatment with mometasone furoate nasal spray plus isotonic saline is not superior to saline alone in elderly patients with rhinitis in respect of improving nasal patency, quality of life, and reducing the intensity of symptoms. TRIAL REGISTRATION: The trial is registered at the Brazilian Clinical Trials Registry (ReBEC) #RBR-498bnq. Registered 05 July 2017.

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Abstract Introduction Oral antihistamines and intranasal corticosteroids have been shown to be effective and safe for the treatment of allergic rhinitis; however, the evidence suggests a level of superiority of corticosteroids, so they should be preferred over the former. Objective To know the prescription profile of two second generation antihistamines (cetirizine and levocetirizine) and two nasal corticosteroids (mometasone and furoateciclesonide) in a cohort of patients with allergic rhinitis, and to compare the clinical outcomes obtained. Methods A cohort study was carried including patients with allergic rhinitis treated with cetirizine, levocetirizine, mometasone furoate or ciclesonide. The improvement was evaluated with the total nasal symptoms score (TNSS). This scale yields results between 0 and 12. Zero indicates absence of symptoms. Results A total of 314 patients completed 12 weeks of follow-up. Seventy-five percent were treated with antihistamines, 20% with corticosteroids, and 5% with a combination of the above. The TNSS median for corticosteroid was 2.5 points; for antihistamines, its was 5 points, and for combination, it was 4 points. We found differences between corticosteroids and antihistamines. Conclusion The prescription percentage of second generation oral antihistamines is higher than that of intranasal corticosteroids. However, patients with allergic rhinitis treated with the second option obtained better control of symptoms.

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Introduction Oral antihistamines and intranasal corticosteroids have been shown to be effective and safe for the treatment of allergic rhinitis; however, the evidence suggests a level of superiority of corticosteroids, so they should be preferred over the former. Objective To know the prescription profile of two second generation antihistamines (cetirizine and levocetirizine) and two nasal corticosteroids (mometasone and furoate-ciclesonide) in a cohort of patients with allergic rhinitis, and to compare the clinical outcomes obtained. Methods A cohort study was carried including patients with allergic rhinitis treated with cetirizine, levocetirizine, mometasone furoate or ciclesonide. The improvement was evaluated with the total nasal symptoms score (TNSS). This scale yields results between 0 and 12. Zero indicates absence of symptoms. Results A total of 314 patients completed 12 weeks of follow-up. Seventy-five percent were treated with antihistamines, 20% with corticosteroids, and 5% with a combination of the above. The TNSS median for corticosteroid was 2.5 points; for antihistamines, its was 5 points, and for combination, it was 4 points. We found differences between corticosteroids and antihistamines. Conclusion The prescription percentage of second generation oral antihistamines is higher than that of intranasal corticosteroids. However, patients with allergic rhinitis treated with the second option obtained better control of symptoms.

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Resumen Introducción: La rinosinusitis aguda (RSA) es frecuente en primer nivel de atención y los pacientes pueden mejorar sin antibióticos.Objetivo: Análisis de costo efectividad de furoato de mometasona spray nasal (FMSN) comparado con amoxicilina en tratamiento de rinosinusitis aguda en México desde punto de vista del Sistema Nacional de Salud. Método: Análisis costo-efectividad comparando FMSN 200 mg dos veces al día y amoxicilina 500 mg tres veces al día. Resultados en términos de eficacia modelados como cambios en sistema de Calificación de Síntomas Mayores (MSS por siglas inglés). MSS consiste en cinco preguntas: rinorrea, goteo retro nasal, congestión, cefalea sinusal y dolor facial. Datos clínicos obtenidos de ensayo clínico aleatorizado. Costos expresados en pesos mexicanos 2016. Se realizó análisis de sensibilidad univariable y multivariables para algunos parámetros utilizados en el modelo. Resultados: Los costos proyectados fueron de $3,261 pesos con FMSN y $3,438 pesos con amoxicilina. FMSN fue asociado con ahorro de costos por paciente de $177 pesos comparado con amoxicilina en un periodo de dos semanas. La tasa incremental de costo-efectividad del FMSN lo ubica como dominante frente a amoxicilina. El análisis de sensibilidad confirma los ahorros globales de costos y la superioridad en términos de la eficacia. Conclusión: En pacientes con rinosinusitis aguda, no complicada, el tratamiento del, FMSN 200 mcg dos veces al día, produjo mejoras significativas de los síntomas en comparación con amoxicilina en pacientes sin infecciones bacterianas y es una alternativa costo efectiva para el Sistema Nacional de Salud Mexicano. Comentario editorial al finalizar el artículo.

Abstract Introduction: Acute rhinosinusitis (RSA) is a common cause of consultation on first level of attention and it can be solved without antibiotics use. Objective: Analysis of cost effectiveness of nasal spray mometasone furoate (NSMF) compared to amoxicillin in treatment of acute rhinosinusitis in Mexico from a National Mexican Health System perspective. Methods: Cost-effectiveness analysis comparing NSMF 200µg twice daily and amoxicillin 500mg three time daily. The effectiveness outcomes of the study were modeled as changes in the Major Symptom Score (MSS). MSS consists of five questions concerning rhinorrhea, post-nasal drip, nasal congestion, sinus headache, and facial pain. Clinical data were obtained from a randomized clinical trial. Cost were expressed in Mexican pesos 2016. Sensitivity analysis was conducted univariable and multivariable for some model parameters. Results: The projected costs were $3,261 pesos with NSMF and $3,438 pesos with amoxicillin. NSMF was associated with a cost savings per patient of $177 pesos versus amoxicillin over a 2 weeks period. The incremental cost-effectiveness ratio for NSMF dominated amoxicillin. The sensitivity analysis confirms overall cost savings and superiority in terms of effectiveness. Conclusion: In patients with non-complicated acute rhinosinusitis NSMF 200 µg twice daily produce significantly an improvement in symptoms compared to amoxicillin in patients without bacterial infections and is a cost-effective alternative for the National Health Mexican System. Editorial comment at the end of this article.

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ABSTRACT INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

Resumo Introdução: A rinite alérgica é considerada a doença respiratória mais prevalente no Brasil e em todo o mundo, com grande impacto na qualidade de vida; além de, afetar a vida social, o sono e também o desempenho na escola e no trabalho. Objetivo: Comparar a eficácia e segurança de duas formulações contendo furoato de mometasona no tratamento da rinite alérgica persistente leve, moderada ou grave por um período de quatro semanas. Método: Trata-se de um estudo nacional aberto de fase III, randomizado, de não inferioridade de comparação do furoato de mometasona em duas apresentações (medicação de controle e fármaco sob investigação). O ponto final primário foi o percentual de pacientes com redução mínima de 0,55 no escore de índice nasal (EIN) após quatro semanas de tratamento. Os desfechos secundários foram: escore NIS total após 4 e 12 semanas de tratamento; escores individuais para sintomas de obstrução nasal, rinorréia, espirros e prurido nasal, bem como escores para prurido, lacrimejamento e hiperemia conjuntival após 4 e 12 semanas de tratamento. O estudo foi registrado em clinicaltrials.gov com o número de referência NCT01372865. Resultados: A análise de eficácia primária demonstrou não inferioridade do fármaco sob investigação em relação à medicação de controle, visto que o limite superior do intervalo de confiança (IC) de 95% para a diferença entre os percentuais de sucesso após quatro semanas de tratamento (12,6%) situava-se abaixo da margem de não inferioridade proporcionada durante a determinação do tamanho da amostra (13,7%). Eventos adversos foram pouco frequentes e de leve intensidade na maioria dos casos. Conclusão: A eficácia e a segurança de um fármaco experimental no tratamento da rinite alérgica persistente foram similares às do produto de referência, o que demonstrou sua não inferioridade.

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INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

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Black henna tattoos have paraphenylenediamine (PPD), which contains a product of herbal origin, which due to its molecular characteristics is capable of inducing, in susceptible individuals, a type IV hypersensitivity reaction. It clinically manifests as a contact dermatitis that usually when it disappears, scarring and hypopigmentation are left in the injured area. Objective: To describe the case of a patient with hypersensitivity to henna tattoo and to present the most relevant phenomena associated with this condition. Case report: The case of a 6 year-old patient with a black henna tattoo on his right leg, who was diagnosed with contact dermatitis probably attributed to PPD, is presented. Mometasone furoate and topical silicone gel treatment was started with good response. Conclusion: Mometasone furoate and silicone gel are a good possible therapeutic option for treating contact dermatitis caused by PPD as the dermatosis was resolved without residual lesions.

Los tatuajes de henna negra son aquellos que contienen parafenilendiamina (PPD), que contienen un producto de origen herbal, que por sus características moleculares es capaz de inducir, en individuos susceptibles, una reacción de hipersensibilidad tipo IV. Se manifiesta clínicamente como una dermatitis de contacto, que generalmente al desaparecer, persiste de manera residual una cicatriz hipertrófica e hipopigmentación en la zona lesionada. Objetivo: Describir el caso de un paciente con hipersensibilidad al tatuaje de henna, y presentar los fenómenos más relevantes asociados a esta patología. Caso clínico: Paciente de 6 años de edad, que se realizó un tatuaje con henna negra en la pierna derecha, en quien se diagnosticó posteriormente una dermatitis de contacto atribuida probablemente a la PPD. Se comenzó tratamiento con furoato de mometasona y gel de silicona con buena respuesta por vía tópica. Conclusión: El furoato de mometasona y gel de silicona son una posible opción terapéutica de utilidad para tratar la dermatitis de contacto causada por el PPD, debido a que la dermatosis se resolvió sin lesiones residuales.

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Introducción. El término fimosis abarca distintas condiciones que van desde la presencia de un anillo fibroso hasta un prepucio asintomático pero no retráctil. Hasta hace algunos años, la circuncisión era la única opción disponible para el manejo de la fimosis. Sin embargo, diversos estudios y ensayos clínicos han evaluado el uso de esteroides tópicos para la liberación del prepucio fimótico. En el presente trabajo se evaluó el efecto del furoato de mometasona al 0.1% como tratamiento en la liberación de adherencias prepuciales y fimosis en niños mexicanos. Métodos. Se realizó un estudio retrospectivo y descriptivo en el que se incluyeron a 129 pacientes de 1 a 8 años de edad, a quienes se les aplicó furoato de mometasona al 0.1% en el prepucio y el glande una vez al día por 4 semanas y se les realizó una sinequiotomía al término del tratamiento. Resultados. Al realizar la sinequiotomía, se logró la retracción total del prepucio en 98% de los casos; de estos, 20% presentó recaída. En términos generales, la eficacia a largo plazo fue de 81% (IC 95% 73-89). Conclusiones. La aplicación tópica de furoato de mometasona al 0.1% fue eficaz para manejar la fimosis y liberar adherencias en el prepucio de niños mexicanos.

Background. In this study we evaluated the effect of mometasone furoate (0.1%) as a nonsurgical treatment of phimosis in Mexican children. Methods. We carried out a retrospective and descriptive study including 129 patients between 1 and 8 years old who were treated with the topical administration of 0.1% mometasone furoate on the prepuce and glans once daily for 4 weeks followed by sinechiotomy at the end of treatment. Results. After sinequiotomy, the foreskin was able to be fully retracted over the glans in 98% of the patients; however, in 20% of patients it returned to the original condition. Overall long-term efficacy was 81% (95% CI: 73-89). Conclusions. Topical administration of mometasone furoate (0.1%) was effective in the detachment of the foreskin of the prepuce from the glans, making it an effective, nonsurgical treatment for phimosis.

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Dermatological inflammatory diseases such as atopic dermatitis, psoriasis and seborrhoeic dermatitis often affect the scalp and the eyebrows. Although there are many dosage forms available, these are particularly critical anatomic regions for application of topical formulations because of the presence of hair. Lotions are therefore the recommended type of drug delivery system for these areas. The presence of hair may limit the application and thus the acceptability of the formulation and its compliance. Because of its low apparent viscosity, lotion application is unpleasant. Gels, given their consistency and adhesiveness, are a suitable alternative to lotions in this situation. The aim of this study was to formulate a stable gel containing mometasone furoate, which is an anti-inflammatory and anti-pruritic corticosteroid, in order to improve topical treatment of scalp dermatitis. In this study, pharmaceutical development, physical-chemical characterization, stability and in vitro permeation studies were performed. In terms of the pH, viscosity, assay and macroscopic and microbiological properties, the gel was stable over the period of study. The in vitro permeation studies allowed the characterization of the mometasone furoate permeation profile for the gel through different membranes. Mometasone furoate presented a slow permeation through the skin. This gel appears safe for topical application.

Afecções dermatológicas do tipo inflamatório como a dermatite atópica, psoríase e dermatite seborreica, afetam freqüentemente o couro cabeludo e sobrancelhas. Apesar de existirem várias formas farmacêuticas para o seu tratamento, apenas as loções são indicadas para estas zonas, mas devido à baixa viscosidade, a aplicação de loções torna-se desagradável. Os geles, pela maior consistência e capacidade de adesão, apresentam-se como alternativa nesta situação. Neste trabalho procedeu-se ao desenvolvimento galênico de um gel com furoato de mometasona, que é um potente corticóide de última geração, com um rácio melhorado de risco/benefício. Foram avaliadas as características físico-químicas, a estabilidade e foram realizados ensaios de permeação in vitro. O gel obtido apresenta características organolépticas e reológicas adequadas ao fim a que se destina tendo-se apresentado estável química, física e microbiologicamente durante o tempo do ensaio. Os estudos de permeação in vitro permitiram caracterizar a formulação através de diferentes membranas. A membrana biológica (pele) não permite uma grande permeação do fármaco o que poderá sugerir que esta formulação é segura para aplicação tópica.

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