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Biomedicine & Pharmacotherapy =... Jun 2023Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese...
Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese medicine, is primarily used for the clinical treatment of AD. In this study, a 2,4-dinitrochlorobenzene-induced AD BALB/c mouse model was established, and a comprehensive pharmacological method was used to determine the pharmacological effects and molecular mechanisms of PAF in the treatment of AD. The results indicated that both PAF gel (PAFG) and PAFG+MF (mometasone furoate) attenuated the severity of AD and reduced the infiltration of eosinophils and mast cells in the skin. Serum metabolomics showed that PAFG combined with MF administration exerted a synergistic effect by remodeling metabolic disorders in mice. In addition, PAFG also alleviated the side effects of thymic atrophy and growth inhibition induced by MF. Network pharmacology predicted that the active ingredients of PAF were flavonoids and exerted therapeutic effects through anti-inflammatory effects. Finally, immunohistochemical analysis confirmed that PAFG inhibited the inflammatory response through the ERβ/HIF-1α/VEGF signaling pathway. Our results revealed that PAF can be used as a natural-source drug with good development prospects for the clinical treatment of AD.
Topics: Mice; Animals; Dermatitis, Atopic; Physalis; Plant Extracts; Flavonoids; Hormones
PubMed: 37003035
DOI: 10.1016/j.biopha.2023.114622 -
Pharmaceutics Mar 2023The aim of the study was to develop a sustained-release varnish (SRV) containing mometasone furoate (MMF) for sinonasal stents (SNS) to reduce mucosa inflammation in the...
The aim of the study was to develop a sustained-release varnish (SRV) containing mometasone furoate (MMF) for sinonasal stents (SNS) to reduce mucosa inflammation in the sinonasal cavity. The SNS' segments coated with SRV-MMF or an SRV-placebo were incubated daily in a fresh DMEM at 37 °C for 20 days. The immunosuppressive activity of the collected DMEM supernatants was tested on the ability of mouse RAW 264.7 macrophages to secrete the cytokines' tumor necrosis factor α (TNFα) and interleukin (IL)-10 and IL-6 in response to lipopolysaccharide (LPS). The cytokine levels were determined by respective Enzyme-Linked Immunosorbent Assays (ELISAs). We found that the daily amount of MMF released from the coated SNS was sufficient to significantly inhibit LPS-induced IL-6 and IL-10 secretion from the macrophages up to days 14 and 17, respectively. SRV-MMF had, however, only a mild inhibitory effect on LPS-induced TNFα secretion as compared to the SRV-placebo-coated SNS. In conclusion, the coating of SNS with SRV-MMF provides a sustained delivery of MMF for at least 2 weeks, maintaining a level sufficient for inhibiting pro-inflammatory cytokine release. This technological platform is, therefore, expected to provide anti-inflammatory benefits during the postoperative healing period and may play a significant role in the future treatment of chronic rhinosinusitis.
PubMed: 36986875
DOI: 10.3390/pharmaceutics15031015 -
Respiratory Medicine May 2023A novel, once-daily, fixed-dose combination of mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) delivered via Breezhaler® is the first inhaled...
Efficacy of once-daily, single-inhaler, fixed-dose combination of mometasone/indacaterol/glycopyrronium in patients with asthma with or without persistent airflow limitation: Post hoc analysis from the IRIDIUM study.
BACKGROUND
A novel, once-daily, fixed-dose combination of mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) delivered via Breezhaler® is the first inhaled corticosteroid/long-acting ꞵ-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) therapy approved for the maintenance treatment of asthma in adults inadequately controlled on ICS/LABA combination. In patients with asthma and persistent airflow limitation (PAL), maximal treatment, especially with combination is suggested. This post hoc analysis of data from the IRIDIUM study assessed the efficacy of MF/IND/GLY in asthma patients with and without PAL.
METHODS
Patients with post-bronchodilator FEV ≤80% of predicted and FEV/FVC ratio of ≤0.7 were categorised as PAL subgroup and the remaining as the non-PAL subgroup. Lung function parameters (FEV, PEF, and FEF) and annualised asthma exacerbations rates were evaluated in both subgroups across the treatment arms: once-daily high-dose MF/IND/GLY (160/150/50 μg), high-dose MF/IND (320/150 μg) and twice-daily high-dose fluticasone/salmeterol (FLU/SAL; 500/50 μg).
RESULTS
Of the 3092 randomised patients, 64% (n = 1981) met the criteria for PAL. Overall, there was no evidence of treatment difference between PAL and non-PAL subgroups (interaction P-value for FEV, FEF, PEF, moderate or severe exacerbations, severe exacerbations and all exacerbations were 0.42, 0.08, 0.43 0.29, 0.35 and 0.12, respectively). In the PAL subgroup, high-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL improved trough FEV (mean difference: 102 mL [P < 0.0001] and 137 mL [P < 0.0001]) and reduced moderate or severe (16% and 32%), severe (25% and 39%) and all exacerbations (19% and 38%), respectively.
CONCLUSIONS
Once-daily fixed-dose MF/IND/GLY was efficacious in asthma patients with and without persistent airflow limitation.
Topics: Adult; Humans; Glycopyrrolate; Mometasone Furoate; Iridium; Pulmonary Disease, Chronic Obstructive; Drug Combinations; Forced Expiratory Volume; Lung; Asthma; Indans; Nebulizers and Vaporizers; Administration, Inhalation; Bronchodilator Agents
PubMed: 36906187
DOI: 10.1016/j.rmed.2023.107172 -
International Journal of Pharmaceutics:... Dec 2023Co-suspension drug-loading technology, namely Aerosphere™, can improve fine particle fraction (FPF) and delivered dose content uniformity (DDCU). However, because of...
Co-suspension drug-loading technology, namely Aerosphere™, can improve fine particle fraction (FPF) and delivered dose content uniformity (DDCU). However, because of its poor drug-loading efficacy, the phospholipid carrier dosage in Aerosphere™ is usually dozens of times greater than that of the drug, resulting in a high material cost and blockage of the actuator. In this study, spray-freeze-drying (SFD) technology was used to prepare inhalable distearoylphosphatidylcholine (DSPC)-based microparticles for pressurized metered-dose inhalers (pMDI). Water-soluble, low-dose formoterol fumarate was used as an indicator to evaluate the aerodynamic performance of the inhalable microparticles. Water-insoluble, high-dose mometasone furoate was used to investigate the effects of drug morphology and drug-loading mode on the drug delivery efficiency of the microparticles. The results demonstrated that DSPC-based microparticles prepared using the co-SFD technology not only achieved higher FPF and more consistent delivered dose than those of drug crystal-only pMDI, but the amount of DSPC was also reduced to approximately 4% of that prepared using the co-suspension technology. This SFD technology may also be used to improve the drug delivery efficiency of other water-insoluble and high-dose drugs.
PubMed: 36896094
DOI: 10.1016/j.ijpx.2023.100158 -
JAMA Pediatrics Apr 2023Intranasal corticosteroids (INCs) remain the first-line treatment of chronic rhinosinusitis (CRS) in both adults and children, despite the lack of evidence regarding... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Intranasal corticosteroids (INCs) remain the first-line treatment of chronic rhinosinusitis (CRS) in both adults and children, despite the lack of evidence regarding their efficacy in the pediatric population. Similarly, their effect on the sinonasal microbiome has not been well documented.
OBJECTIVE
To assess the clinical, immunological, and microbiological effects of 12 weeks of an INC in young children with CRS.
DESIGN, SETTING, AND PARTICIPANTS
This open-label randomized clinical trial was performed in a pediatric allergy outpatient clinic in 2017 and 2018. Children aged 4 to 8 years with CRS diagnosed by a specialist were included. Data were analyzed from January 2022 to June 2022.
INTERVENTIONS
Patients were randomized to receive intranasal mometasone in an atomizer for 12 weeks (1 application per nostril, once per day) and supplemental 3-mL sodium chloride (NaCl), 0.9%, solution in a nasal nebulizer once a day for 12 weeks (INC group) or 3-mL NaCl, 0.9%, solution in a nasal nebulizer once a day for 12 weeks (control group).
MAIN OUTCOMES AND MEASURES
Measures taken both before and after treatment included the Sinus and Nasal Quality of Life Survey (SN-5), a nasopharynx swab for microbiome analysis by next-generation sequencing methods, and nasal mucosa sampling for occurrence of innate lymphoid cells (ILCs).
RESULTS
Of the 66 children enrolled, 63 completed the study. The mean (SD) age of the cohort was 6.1 (1.3) years; 38 participants (60.3%) were male and 25 (39.7%) were female. The clinical improvement reflected by reduction in SN-5 score was significantly higher in the INC group compared with the control group (INC group score before and after treatment, 3.6 and 3.1, respectively; control group score before and after treatment, 3.4 and 3.8, respectively; mean between-group difference, -0.58; 95% CI, -1.31 to -0.19; P = .009). The INC group had a greater increase in nasopharyngeal microbiome richness and larger decrease in nasal ILC3 abundance compared with the control group. A significant interaction was observed between change in microbiome richness and the INC intervention on the prediction of significant clinical improvement (odds ratio, 1.09; 95% CI, 1.01-1.19; P = .03).
CONCLUSIONS AND RELEVANCE
This randomized clinical trial demonstrated that treatment with an INC improved the quality of life of children with CRS and had a significant effect on increasing sinonasal biodiversity. Although further investigation is needed of the long-term efficacy and safety of INCs, these data may reinforce the recommendation of using INCs as a first-line treatment of CRS in children.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03011632.
Topics: Adult; Child; Male; Humans; Female; Child, Preschool; Quality of Life; Sodium Chloride; Immunity, Innate; Nasal Polyps; Rhinitis; Lymphocytes; Adrenal Cortex Hormones; Sinusitis; Chronic Disease; Treatment Outcome
PubMed: 36848113
DOI: 10.1001/jamapediatrics.2022.6172 -
Indian Journal of Otolaryngology and... Dec 2022Aims to evaluate quality of life in paediatric SDB due to adenotonsillar hypertrophy and efficacy of treatment modalities (medical and surgical) by using OSA-18...
Aims to evaluate quality of life in paediatric SDB due to adenotonsillar hypertrophy and efficacy of treatment modalities (medical and surgical) by using OSA-18 questionnaire. Prospective study, conducted from April 2019 to June 2019, including 42 patients with clinical features suggestive of SDB due to adenotonsillar hypertrophy, in age group of 3-15 years. Nasopharyngoscopy was done to grade adenoid hypertrophy. OSA-18 QOL questionnaire was recorded in all patients and depending upon the severity of impact of QOL and grades of adenoid hypertrophy, patients were categorized into two groups. Group 1 received medical treatment and group 2 underwent adenotonsillectomy. Questionnaire was again recorded after 4 weeks. Pretreatment and post-treatment total mean and individual domain scores were compared. Paired tests was used to evaluate results. Group 1 included 16 children with mild to moderate impact and received medical management. Pretreatment mean OSA-18 score of 70.31 was improved to 33.5. Group 2 enrolled 26 patients with severe impact, were subjected to adenotonsillectomy. Pretreatment and post-treatment mean score were 95.88 and 24.92 respectively. Both groups showed statistically significant improvement in all individual domains and total mean OSA-18 scores indicating improvement in QOL after treatment and efficacy of medical management for mild-moderate SDB and surgery for severe cases. OSA-18 questionnaire is self-administered and disease specific screening tool for early diagnosis and evaluation of QOL before and after treatment. It also helps to categorize patients for advocating appropriate treatment and to evaluate efficacy of treatment modalities.
PubMed: 36742702
DOI: 10.1007/s12070-019-01757-0 -
Journal of Healthcare Engineering 2023[This retracts the article DOI: 10.1155/2022/3495099.].
Retracted: Treatment Effect of Mometasone Furoate Cream on Lichen Sclerosus et Atrophicus of External Genitalia in Boys and Its Correlation with Toll-Like Receptor 4 and Myeloid Differentiation Factor 88.
[This retracts the article DOI: 10.1155/2022/3495099.].
PubMed: 36741875
DOI: 10.1155/2023/9764362 -
Journal of Asthma and Allergy 2023Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler have been... (Review)
Review
Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma.
BACKGROUND
Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment.
OBJECTIVE
Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies.
METHODS
The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations.
RESULTS
Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study.
CONCLUSION
These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.
PubMed: 36714049
DOI: 10.2147/JAA.S392975 -
Patient Preference and Adherence 2023Combination intranasal corticosteroid and antihistamine sprays are a first-line treatment option for allergic rhinitis (AR), of which Azelastine Hydrochloride and...
Patient Satisfaction and Sensory Attributes of Nasal Spray Treatments of Olopatadine Hydrochloride/Mometasone Furoate Monohydrate and Azelastine Hydrochloride/Fluticasone Propionate for Allergic Rhinitis in Australia - An Observational Real-World Clinical Study.
PURPOSE
Combination intranasal corticosteroid and antihistamine sprays are a first-line treatment option for allergic rhinitis (AR), of which Azelastine Hydrochloride and Fluticasone Propionate nasal spray (AZE/FLU; Dymista), and Olopatadine Hydrochloride and Mometasone Furoate Monohydrate nasal spray (OLO/MOM; Ryaltris) are currently registered in Australia. As it is not known how patients value treatment attributes of current combination nasal sprays, this observational, real-world clinical study aimed to understand patients' satisfaction with, and importance of, treatment attributes of OLO/MOM and AZE/FLU using an Anchored Best-Worst Scaling (ABWS) exercise.
PARTICIPANTS AND METHODS
Four hundred and twenty-six adults in Australia with moderate to severe AR using either OLO/MOM or AZE/FLU completed an online survey incorporating an ABWS with 11 domains: 7 sensory (immediate taste of medication, aftertaste of medication, smell of medication, irritation to your nose, urge to sneeze, dripping out your nose/down your throat, dryness of your nose/throat) and 4 treatment-related (convenience, fast acting, duration of effect, and AR symptom control). The ABWS involved rescaling individual BWS scores using anchored ratings (0-10) for most and least satisfied/important domains to create a total satisfaction index (TSI) (0-100) to be compared across groups. Statistical comparisons were completed using ANOVA (TSI) and MANOVA (individual domains).
RESULTS
Participants using OLO/MOM ( = 68.26, = 1.39) had significantly higher TSI than participants using AZE/FLU (=62.78, = 0.70) ( < 0.001), significantly higher satisfaction on 7 of 11 domains and regarded 8 of 11 domains as significantly more important compared to participants using AZE/FLU (all < 0.05). Preferred domains were predominantly sensory attributes.
CONCLUSION
Current findings showed that participants using OLO/MOM were more satisfied with their overall treatment compared to participants using AZE/FLU, particularly with sensory attributes, thus highlighting the suitability of OLO/MOM for people with AR who value sensory attributes. Prescribers of AR treatments are encouraged to discuss treatment attributes with patients to facilitate shared decision-making.
PubMed: 36687019
DOI: 10.2147/PPA.S389875 -
Frontiers in Cell and Developmental... 2022The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal...
Designing of SiO mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression.
The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol-gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect.
PubMed: 36684440
DOI: 10.3389/fcell.2022.1026477