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Molecules (Basel, Switzerland) Nov 2023Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to...
Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.
Topics: Humans; Mometasone Furoate; Pregnadienediols; Asthma; Acylation
PubMed: 38067588
DOI: 10.3390/molecules28237859 -
Biomedicines Sep 2023Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and...
Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and neck squamous cell carcinoma (HNSCC) is still unclear. This study aimed to evaluate the inhibitory effect of MF against HNSCC and investigate its underlying mechanisms. Cell viability, colony formation, cell cycle and cell apoptosis were analyzed to explore the effect of MF on HNSCC cells. A xenograft study model was used to investigate the effect of MF on HNSCC in vivo. The core targets of MF for HNSCC were identified using network pharmacology analysis, TCGA database analysis and real-time PCR. Molecular docking was performed to determine the binding energy. Protein tyrosine phosphatase non-receptor type 11 (PTPN11)-overexpressing cells were constructed, and then, the cell viability and the expression levels of proliferation- and apoptosis-related proteins were detected after treatment with MF to explore the role of PTPN11 in the inhibitory effect of MF against HNSCC. After cells were treated with MF, cell viability and the number of colonies were decreased, the cell cycle was arrested and cell apoptosis was increased. The xenograft study results showed that MF could inhibit cell proliferation via promoting cell apoptosis in vivo. PTPN11 was shown to be the core target of MF against HNSCC via network pharmacology analysis, TCGA database analysis and real-time PCR. The molecular docking results revealed that PTPN11 exhibited the strongest ability to bind to MF. Finally, MF could attenuate the effects of increased cell viability and decreased cell apoptosis caused by PTPN11 overexpression, suggesting that MF can inhibit the progression of HNSCC by regulating PTPN11. MF targeted PTPN11, promoting cell cycle arrest and cell apoptosis, and consequently exerting effective anti-tumor activity.
PubMed: 37892971
DOI: 10.3390/biomedicines11102597 -
Drug Delivery and Translational Research Nov 2023Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to...
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.
Topics: Humans; Mometasone Furoate; Zein; Caco-2 Cells; Nanoparticles; Drug Carriers
PubMed: 37208563
DOI: 10.1007/s13346-023-01367-y -
International Journal of Nanomedicine 2023We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local...
PURPOSE
We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local absorption compared to traditional nasal MF formulations (CA-MF).
METHODS
MF nanocrystal dispersions (MF-NPs) were prepared by bead milling MF microcrystal dispersions (MF-MPs) consisting of MF, 2-hydroxypropyl-β-cyclodextrin, methylcellulose, and purified water. Pluronic F-127 combined with methylcellulose, Pluronic F-68, or carbopol was used as a base for in situ gelation (thickener). MF concentrations were measured using high-performance liquid chromatography, and nasal absorption of MF was evaluated in 6 week-old male Institute of Cancer Research (ICR) mice.
RESULTS
The particle size range of MF prepared with the bead mill treatment was 80-200 nm, and the nanoparticles increased the local absorption of MF, which was higher than that of CA-MF and MF-MPs. In addition, unlike the results obtained in the small intestine and corneal tissue, the high absorption of nanocrystalline MF in the nasal mucosa was related to a pathway that was not derived from energy-dependent endocytosis. Moreover, the application of the in situ gelling system attenuated the local absorption of MF-NPs, owing to a decrease in drug diffusion in the dispersions.
CONCLUSION
We found that nanoparticulation of MF enhances local intranasal absorption, and nasal bioavailability is higher than that of CA-MF. In addition, we demonstrate that viscosity regulation is an important factor in the design of nasal formulations based on MF nanocrystals. These findings provide insights for the design of novel nanomedicines with enhanced nasal bioavailability.
Topics: Male; Animals; Mice; Mometasone Furoate; Nasal Absorption; Nasal Mucosa; Methylcellulose
PubMed: 37841023
DOI: 10.2147/IJN.S430952 -
Pulmonary Therapy Sep 2023Suboptimal adherence to inhaled asthma therapy is associated with poor clinical outcomes. Digital companion paired inhaler devices record medication use and provide...
INTRODUCTION
Suboptimal adherence to inhaled asthma therapy is associated with poor clinical outcomes. Digital companion paired inhaler devices record medication use and provide reminders, thereby improving treatment adherence and asthma outcomes. This analysis assessed the impact of indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF) Breezhaler digital companion on medication adherence and symptom control in adults with asthma from Germany.
METHODS
This retrospective analysis included adults (≥ 18 years) with asthma and prescribed Breezhaler digital companion. Assessments included: mean medication adherence (number of puffs taken/prescribed × 100) and change in Asthma Control Test (ACT) scores [well controlled (≥ 20), not well controlled (15-20) and poorly controlled (≤ 15)] at 1 month after the first ACT (second ACT). The percent of patients with ≥ 80% medication adherence (days 16-30 and 76-90) and the change in ACT (baseline and ≥ 30 days) were analysed.
RESULTS
Of the 163 patients with 90 days data, ≥ 80% medication adherence was achieved in 82.8% and 72.4% of patients at months 1 and 3, respectively. Change in asthma control was examined in ~ 60% (n = 97) of patients who completed ≥ 2 ACTs through the application. At baseline, 33.0% of patients were well controlled and 53.6% were well controlled at second ACT. Furthermore, 43.3% patients reported very poor control at baseline which decreased to 22.7% at second ACT.
CONCLUSION
The use of IND/GLY/MF (Breezhaler) with a digital companion (sensor + application) may be associated with improved symptom control and high level of controller medication adherence in patients with asthma.
PubMed: 37120785
DOI: 10.1007/s41030-023-00225-z -
Acta Biochimica Polonica Sep 2023This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients with moderate and severe AR treated at our hospital between January 2017 and August 2020 were recruited as subjects for this study. The patients were randomly divided into control and experimental groups, with 70 patients in each group. Mometasone nasal spray was used in both groups, and vitamin D was administered to the experimental group for four weeks. The total nasal symptom scores (TNSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to assess the efficacy of treatment. T lymphocyte subsets (CD3+, CD4+ and CD8+) and serum anti-inflammatory and proinflammatory cytokines such as interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were analyzed. The incidence of adverse reactions was recorded. Serum vitamin D levels were lower in patients with AR. After 4 weeks of treatment, total TNSS scores, T lymphocyte subsets (CD3+, CD4+), CD4+/CD8+ ratio, TNF-α, and total RQLQ scores were significantly reduced compared to the initial testing (P<0.05) in the two groups; CD8+, IFN-γ, and IL-10 levels as well as serum vitamin D were significantly increased compared to the initial test (P<0.05). The improvement in these parameters in the experimental group was significantly greater than that in the control group (P<0.05), except for sneezing and eye symptoms in the TNSS and RQLQ scores. It was concluded that vitamin D supplementation improves the therapeutic effect of mometasone nasal spray on AR and is thus recommended as an adjuvant therapy for moderate and severe AR.
Topics: Humans; Mometasone Furoate; Interleukin-10; Nasal Sprays; Quality of Life; Tumor Necrosis Factor-alpha; Rhinitis, Allergic; Vitamins; Vitamin D; Interferon-gamma; Dietary Supplements
PubMed: 37716008
DOI: 10.18388/abp.2020_6637 -
Asian Pacific Journal of Allergy and... Dec 2023Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated.
OBJECTIVE
To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context.
METHODS
The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties.
RESULTS
13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy.
CONCLUSIONS
FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.
Topics: Humans; Rhinitis, Allergic, Seasonal; Cost-Effectiveness Analysis; Rhinitis, Allergic; Administration, Intranasal; Adrenal Cortex Hormones; Mometasone Furoate; Anti-Allergic Agents; Treatment Outcome
PubMed: 37874315
DOI: 10.12932/AP-070823-1669 -
European Review For Medical and... Feb 2024Endoscopic evaluation becomes difficult when excessive secretion/hypersalivation occurs in the upper airway. Intranasal corticosteroids and antihistamines reduce...
OBJECTIVE
Endoscopic evaluation becomes difficult when excessive secretion/hypersalivation occurs in the upper airway. Intranasal corticosteroids and antihistamines reduce symptoms of rhinorrhea and nasal congestion. For this reason, in our study, we aimed to examine the effects of mometasone furoate and azelastine on both the amount of secretion and upper airway obstruction in terms of possible benefits during drug-induced sleep endoscopy (DISE).
PATIENTS AND METHODS
A total of 92 patients participated in the study [69 (75%) were males and 23 (25%) were females]. Three groups in Group 1 used intranasal mometasone furoate for 30 days, Group 2 used intranasal azelastine for 30 days, and Group 3 did not use any nasal spray for 30 days. Then, DISE was performed on all patients on the 30th day. Upper airway obstructions detected in DISE were interpreted according to the VOTE classification. Furthermore, the amount of secretion and patients' tolerance levels observed during DISE were also assessed.
RESULTS
Multilevel obstruction was detected in 94.5% of all patients participating in the study. Tolerance was poor in 18 (19.5%) of the patients participating in the study. Better DISE tolerance was determined in the female gender. DISE tolerance was also better in underweight and normal-weight patients (BMI < 25).
CONCLUSIONS
This study first investigated nasal mometasone furoate and azelastine on DISE. This study showed that prior use of nasal mometasone furoate or azelastine before DISE did not affect the amount of secretion, tolerance level, severity, and configuration of obstruction.
Topics: Male; Humans; Female; Mometasone Furoate; Nose; Endoscopy; Sleep; Phthalazines
PubMed: 38436176
DOI: 10.26355/eurrev_202402_35464 -
EClinicalMedicine Jul 2023Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin...
Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.
BACKGROUND
Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP.
METHODS
A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398.
FINDINGS
Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related.
INTERPRETATION
These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP.
FUNDING
KeyMed Biosciences (Chengdu) Limited.
PubMed: 37483544
DOI: 10.1016/j.eclinm.2023.102076 -
Otolaryngologia Polska = the Polish... Dec 2023A novel strategy for the treatment of allergic rhinitis results from the innovative combination of antihistamine and intranasal corticosteroid drugs. By combining two...
A novel strategy for the treatment of allergic rhinitis results from the innovative combination of antihistamine and intranasal corticosteroid drugs. By combining two preparations with different mechanism of action, this novel approach facilitates quick and effective controls of all upper respiratory tract allergy symptoms. The article presents the results of a study of olopatadine hydrochloride and mometasone furoate fixed-dose combination (GSP301) administered intranasally from a spray formulation, with an attempt at positioning the treatment within the ARIA and EPOS guidelines.
Topics: Humans; Mometasone Furoate; Olopatadine Hydrochloride; Administration, Intranasal; Sinusitis; Female; Male; Adult; Anti-Allergic Agents; Drug Combinations; Middle Aged; Treatment Outcome; Rhinitis, Allergic; Rhinitis; Rhinosinusitis
PubMed: 38706259
DOI: 10.5604/01.3001.0054.0941