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Abstract Budesonide (BDS) a steroid-based anti-inflammatory drug widely prescribed for various diseases, has a low aqueous solubility. In this study, we investigated cosolvency approach to study the thermodynamic specifications related to the solubility of BDS at the temperature range of 293.2–313.2 K in (1-propanol + water) mixtures applying the shaking flask method. The predictive power of different mathematical models for experimental data in the cosolvency systems was evaluated. For this purpose, the linear and nonlinear mathematical equations such as van’t Hoff model (as a linear model), Buchowski-Ksiazczak equation (as a non-linear), CNIBS/R–K and MRS models (as a linear model for solvent composition at an isothermal condition), modified Wilson model (as a non-linear model for isothermal condition), the Jouyban-Acree model (as a model that considers temperature and solvent composition), and Jouyban-Acree-van’t Hoff model (as a model with no further input data) were studied. Also, the Williams-Amidon excess Gibbs energy model was investigated. In addition, the related apparent thermodynamics of the BDS dissolution process in the desired temperature such as Gibbs free energy, enthalpy, and entropy, were computed by the corresponding equations. Moreover, based on the inverse Kirkwood-Buff integrals, it is demonstrated that BDS is preferentially solvated by water in water-rich mixtures. The accuracy of the fitness was evaluated with mean relative deviations (MRDs%) for back-calculated molar BDS solubility data. The result showed that the maximum solubility of BDS was obtained at 0.7 mass fraction of 1-propanol at all temperatures. Thermodynamic studies demonstrated that BDS dissolution procedures were obtained as endothermic and entropy-driven in almost all cases. The overall MRDs% values for the back-computed BDS solubility in the aqueous mixture of 1-propanol based on van’t Hoff model, Buchowski-Ksiazczak equation, CNIBS/R–K model, modified Wilson model, Jouyban-Acree model, Jouyban-Acree-van’t Hoff model, MRS model, and Williams-Amidon excess Gibbs energy model were found 1.93%, 1.80%, 11.68%, 33.32%, 12.30%, 9.24%, 10.70%, and 6.57%, respectively. Graphical Abstract

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals with severe and long-standing asthma. Here we explored the potential link between PDAC and the glucocorticoid (GC) budesonide, a first-line therapy to treat asthma. Methods We tested the effect of budesonide and the classical GCs on the morphology, proliferation, migration and invasiveness of patient-derived PDAC cells and pancreatic cancer cell lines, using 2D and 3D cultures in vitro. Furthermore, a xenograft model was used to investigate the effect of budesonide on PDAC tumor growth in vivo. Finally, we combined genome-wide transcriptome analysis with genetic and pharmacological approaches to explore the mechanisms underlying budesonide activities in the different environmental conditions. Results We found that in 2D culture settings, high micromolar concentrations of budesonide reduced the mesenchymal invasive/migrating features of PDAC cells, without affecting proliferation or survival. This activity was specific and independent of the Glucocorticoid Receptor (GR). Conversely, in a more physiological 3D environment, low nanomolar concentrations of budesonide strongly reduced PDAC cell proliferation in a GR-dependent manner. Accordingly, we found that budesonide reduced PDAC tumor growth in vivo. Mechanistically, we demonstrated that the 3D environment drives the cells towards a general metabolic reprogramming involving protein, lipid, and energy metabolism (e.g., increased glycolysis dependency). This metabolic change sensitizes PDAC cells to the anti-proliferative effect of budesonide, which instead induces opposite changes (e.g., increased mitochondrial oxidative phosphorylation). Finally, we provide evidence that budesonide inhibits PDAC growth, at least in part, through the tumor suppressor CDKN1C/p57Kip2. Conclusions Collectively, our study reveals that the microenvironment influences the susceptibility of PDAC cells to GCs and provides unprecedented evidence for the anti-proliferative activity of budesonide on PDAC cells in 3D conditions, in vitro and in vivo. Our findings may explain, at least in part, the reason for the lower occurrence of pancreatic cancer in asthmatic patients and suggest a potential suitability of budesonide for clinical trials as a therapeutic approach to fight pancreatic cancer.

Abstract Background Respiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants. Objective This study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS. Method An outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18. Results Overall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p

Yueying Niu,1 Mengqing Cao,1 Shumin Li,1 Juanfen Mo,2 Ziyi Zhu,1 Haiqin Wang1 1Department of Respiratory Medicine, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 2The Key Laboratory, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Haiqin Wang; Ziyi Zhu, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.com; zhuziyi1986@163.comObjective: To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy.Methods: This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared.Results: In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-β 1, and IgE and number of eosinophils significantly decreased (P < 0.05). There were statistically significant differences in the IL-6 and TGF-β 1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P< 0.05). The receiver operating characteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-β 1 at T1, T2, and T3.Conclusion: Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-β 1 can be used as early predictors of budesonide inhalation efficacy.Keywords: budesonide, cough variant asthma, cytokines, IL-6, TGF-β 1

Background: The purpose of this work was to complex budesonide with cyclodextrin-based nanosponges to improve its solubility and stability. The current study focused on polysaccharide systems that have undergone minimal chemical alteration and have been used to target the colon. These targeted delivery and polysaccharide-based complexation methods are anticipated to aid in the creation of medication formulations for disorders affecting the colon, such as colorectal cancer. The goal of the current work was to use a Quality by Design (QbD) strategy to create budesonide-loaded nanosponges. The system consisted of nanosponges loaded with budesonide. Methods: Nanosponges were formulated through microwave-assisted synthesis. Studies on drug release were conducted with a method changing power of hydrogen (pH) with enzyme. Quality by Design-based optimization with a 32 full factorial design was applied for the optimization of the process parameters including the β-cyclodextrin:diphenyl carbonate ratio and the reaction time. Responses were measured for three dependent variables: practical yield, percentage drug release, and percentage drug release at the fifth hour. Results and Conclusions: The optimization model indicated a yield of 76.21%, a percentage drug release at the fifth hour of 24.61%, and a total drug release after 7 hours of 87.58%. The observed responses of the optimized process closely matched the predicted values. The above budesonide-loaded nanosponge formulations provide a targeted medicine for the colon and may be an effective method for treating colonic illness.

Xu Zuo,1 Yinuo Gu,1 Xiaoping Guo,1 Wenxue Zheng,1 Haoyu Zheng,1 Yiming An,1 Caina Xu,2,3 Fang Wang1,3 1Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Biochemistry, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China; 3Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Caina Xu; Fang Wang, Email xucaina@jlu.edu.cn; wf@jlu.edu.cnPurpose: Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment.Methods: BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed.Results: The particle size, PDI, and zeta potential of BUD-LNPs were 127.63± 1.33 nm, 0.27± 0.02, and 3.33± 0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD.Conclusion: BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.Keywords: liposomal nanoparticles, asthma, budesonide, pulmonary delivery, nano-vehicles

Background/Objectives: Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. Methods: This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. Results: A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. Conclusions: This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Recombinant AAV (rAAV) vectors are increasingly favored for gene therapy due to their useful features of vectorology, such as transfection of dividing and nondividing cells, the presence of tissue-specific serotypes, and biosafety considerations. This study investigates the impact of commonly used therapeutic drugs—acetaminophen, budesonide, and simvastatin—on rAAV transduction efficiency in HEK-293 cells. Cells were transduced with an AAV mosaic vector under the control of a cytomegalovirus (CMV) promoter encoding green fluorescent protein (GFP). Transduction efficiency was assessed by qPCR and fluorescent microscopy. Analysis of functional interactions between genes potentially involved in rAAV transduction in drug-exposed cells was also performed. This study showed a clear effect of drugs on rAAV transmission. Notably, acetaminophen enhanced transduction efficiency by 9-fold, while budesonide and simvastatin showed 2-fold and 3-fold increases, respectively. The gene analysis illustrates the possible involvement of genes related to cell membranes in the potentiation of rAAV transduction induced by the drugs under investigation. Attention should be paid to S100A8, which is a common drug-modified gene for drugs showing anti-inflammatory effects (budesonide and simvastatin), demonstrating an interaction with the gene encoding the receptor for AAV (HGFR). This study underscores the significance of assessing rAAV pharmacokinetics/pharmacodynamics (PKs/PDs) and drug–gene therapy interactions in optimizing gene therapy protocols.

Abstract Background Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn’s disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland. Methods This retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups. Results Overall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0–98.0] and 95 [70.0–98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%). Conclusions In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD. Trial registration Not applicable.

Objectives: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. Methods: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. Results: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). Conclusion: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Background: Despite numerous clinical strategies performed over the years, Bronchopulmonary dysplasia (BPD) still remains a common disease with considerable long-term adverse effects in very premature infants. This study investigated the effect of budesonide-instilled surfactant on the incidence of BPD in preterm infants.Methods: In this clinical trial, a total of 190 neonates with a gestational age of less than 30 weeks, who were identified as candidates for surfactant therapy, were randomly assigned to two groups. The control group (S) received surfactant at a dosage of 200 mg/kg for the initial dose and 100 mg/kg for subsequent doses. In cases where it was deemed necessary (n=95), the intervention group (BS) received surfactant along with budesonide, instilled once at a dose of 0.25 mg/kg (n=95). The primary outcome was the occurrence of BPD, and the combined incidence of BPD and death Secondary outcomes encompassed other complications related to prematurity and adverse effects associated with corticosteroid use.Results: Demographic characteristics of the neonates were comparable between the two groups. Although a slight reduction was seen in the incidence of BPD in the group receiving budesonide, BPD rates remained statistically unchanged after the intervention (48.4% in the BS group vs 50.5% in the S group, P value = 0.772). The combined outcome of BPD and death was insignificantly different between the two groups (61.1% in the BS group vs. 63.2% in the S group, P value = 0.765). The addition of budesonide resulted in an increased incidence of sepsis and pneumothorax in the control group. However, secondary outcomes such as IVH (Inra ventricular Hemorrhage(, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and hyperglycemia were unaffected. Duration of total parenteral nutrition and hospitalization time were longer in the BS group than in the S group.Conclusion: The addition of budesonide to surfactant in very premature neonates at gestational age

Background: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. Methods: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. Results: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04–1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08–2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64–1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43–1.56; I2 = 0%). Conclusions: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs fail to provide sufficient oxygen to the body’s vital organs. It is commonly associated with COVID-19 patients. Severe cases of COVID-19 can lead to lung damage and organ failure due to an immune response in the body. To mitigate these effects, corticosteroids, which are known for their anti-inflammatory properties, have been suggested as a potential treatment option. The primary focus of this study was to assess the impact of various corticosteroid administration methods on the outcomes of patients with COVID-19. Methods: The current study was conducted on COVID-19 patients divided into three groups. The first group was administered 6 mg of intravenous (IV) dexamethasone; the second group received 1 mg/kg of IV methylprednisolone (methylprednisolone); and the third group received budesonide respirable solution at a dosage of 1mg twice daily. The neubilizer used was a vibrating mesh nebulizer (VMN). All patients received standard care. We found that dexamethasone administered intravenously led to a significant reduction in C-reactive protein levels, surpassing the effectiveness of both IV methylprednisolone and inhaled budesonide. Oxygen saturation without mask change over time showed statistically significant differences (p = 0.004) in favor of the budesonide and dexamethasone groups for all days. Individuals who received methylprednisolone showed a significant decrease in mortality rate and an extended survival duration, with statistical significance observed at p = 0.024. The rest of the parameters, including ferritin, lymphocytes, total leukocyte count, platelets, hemoglobin, urea, serum potassium, serum sodium, serum creatinine, serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, uric acid, albumin, globulin, erythrocyte sedimentation rate, international normalized ratio, oxygen saturation with flow, and oxygen flow, showed no statistically significant differences between the three drugs. In conclusion, treatment with IV methylprednisolone (1 mg/kg) resulted in a shorter hospital stay, decreased reliance on ventilation, and improved health outcomes for COVID-19 patients compared to using dexamethasone at a daily dosage of 6 mg or budesonide respirable solution at a dosage of 1mg twice daily.

Background: Severe and moderate asthma attacks are among the major causes of children’s visits to emergency departments. Objectives: The present systematic review is conducted to assess the effectiveness of inhaled budesonide on hospitalization and clinical presentations in children with asthma. Methods: A search was conducted on six English databases from 2000 to 2022. Quality assessment was done using Cochrane Collaboration’s tool for Assessing the Risk of Bias, and heterogeneity was assessed using I2. The risk of bias was calculated using a funnel plot and Begg and Egger tests. The data were analyzed using RevMan 5, and random effects, the risk ratio and means difference were reported with a 95% confidence interval. Results: Totally, 1380 studies were identified. After the screening, ten studies with a sample size of 1859 were included in the systematic review. The asthma scores were improved following budesonide administration in 10 studies. Compared to the placebo, the effects of budesonide on hospitalization rate were not statistically significant, but they were statistically significant with zero heterogeneity compared to other corticosteroids. Compared to the placebo or oral corticosteroids, there were no significant differences in heart rate, respiratory rate, and oxygen saturation after budesonide administration. Conclusion: The effects of inhaled corticosteroids were similar to other oral corticosteroids and the placebo. Considering the high heterogeneity of the studies, future studies with larger sample sizes and longer follow-ups are recommended.

Background: Although adherence to inhaled medication is critically important for treatment efficiency, around half of patients taking these drugs are non-adherent or make critical errors when using their delivery device. Segmental hair analysis might be a valuable tool for therapeutic monitoring because hair concentrations reflect exposure from month to month. The objective of the present proof-of-concept study was to establish the feasibility of segmental hair analysis of inhaled budesonide and formoterol in asthma patients.Methods: We conducted a prospective, open-label, interventional study of adult patients being treated with budesonide/formoterol for controlled, moderate-to-severe asthma (CorticHair, NCT03691961). Asthma control, lung function, and medication adherence were recorded. Hair samples were taken 4 months after enrolment and cut into four 1 cm segments.Results: Samples were available from 21 patients (20 women; median age: 53; median budesonide dose: 600 μg/d). Budesonide and formoterol were detected in samples from 18 to 13 patients, respectively. The median hair concentrations were 6.25 pg/mg for budesonide and 0.9 pg/mg for formoterol. The intrapatient coefficient of variation between hair segments was 21% for budesonide and 40% for formoterol. Pearson’s coefficients for the correlations between the hair concentration and the self-reported drug dose and the prescribed drug dose were respectively 0.42 (p = 0.08) and 0.29 (p = 0.25) for budesonide and 0.24 (p = 0.44) and 0.17 (p = 0.57) for formoterol.Conclusion: Segmental hair analysis of inhaled medications was feasible, with low intrapatient variability. This innovative, non-invasive means of assessing monthly drug exposure might help physicians to personalize drug regimens for patients with difficult-to-treat asthma.

Background: Allergic rhinitis (AR) is a common immunoglobulin (Ig) E-mediated disease. This study aimed to evaluate the gene expression levels of class 4 semaphorins and their receptors in AR patients before and after treatment with budesonide and fexofenadine (B/F) compared to fluticasone propionate and fexofenadine (FP/F). Methods: In this study, 29 AR patients (age 34.4 ± 1.2 years, 18 men and 11 women) were treated with B/F, and 24 AR patients (age 32.8 ± 1.9 years, 15 men and 9 women) were treated with FP/F for one month. Before and after treatment, peripheral blood samples were taken from patients. The expression levels of SEMA4A, SEMA4C, SEMA4D, Plexin-B2, and Plexin-D1 genes were measured using the qPCR method. In addition, the serum levels of IgE were measured using an enzyme-linked immunosorbent assay (ELISA). Results: The expression levels of SEMA4A (P = 0.011), 4C (P = 0.017), Plexin-B2 (P = 0.0005), and Plexin-D1 (P = 0.008) remarkably increased in AR patients treated with B/F. Our results show a significant reduction in the gene expression levels of SEMA4A (P = 0.002), 4C (P = 0.014), 4D (P = 0.003), Plexin-B2 (P = 0.033), and Plexin-D1 (P = 0.035) after treatment with FP/F. The serum levels of IgE increased in FP/F treated group (P = 0.017) and conversely decreased in the treated group with B/F (P = 0.019). Moreover, the percentages of eosinophils were reduced in both FP/F and B/F groups (P = 0.015 and P = 0.0001, respectively). Conclusion: In conclusion, concomitant use of fexofenadine and fluticasone propionate reduced SEMA4A, 4C, 4D, Plexin-B2, and Plexin-D1, while the SEMA4A, 4C, Plexin-B2, and Plexin-D1 gene expression levels were increased in the patient group treated with B/F.

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (> 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

AbstractInflammatory bowel disease (IBD) is one of the most common intestinal disorders, with increasing global incidence and prevalence. Numerous therapeutic drugs are available but require intravenous administration and are associated with high toxicity and insufficient patient compliance. Here, an oral liposome that entraps the activatable corticosteroid anti-inflammatory budesonide was developed for efficacious and safe IBD therapy. The prodrug was produced via the ligation of budesonide with linoleic acid linked by a hydrolytic ester bond, which was further constrained into lipid constituents to form colloidal stable nanoliposomes (termed budsomes). Chemical modification with linoleic acid augmented the compatibility and miscibility of the resulting prodrug in lipid bilayers to provide protection from the harsh environment of the gastrointestinal tract, while liposomal nanoformulation enables preferential accumulation to inflamed vasculature. Hence, when delivered orally, budsomes exhibited high stability with low drug release in the stomach in the presence of ultra-acidic pH but released active budesonide after accumulation in inflamed intestinal tissues. Notably, oral administration of budsomes demonstrated favorable anti-colitis effect with only ∼7% mouse body weight loss, whereas at least ∼16% weight loss was observed in other treatment groups. Overall, budsomes exhibited higher therapeutic efficiency than free budesonide treatment and potently induced remission of acute colitis without any adverse side effects. These data suggest a new and reliable approach for improving the efficacy of budesonide. Our in vivo preclinical data demonstrate the safety and increased efficacy of the budsome platform for IBD treatment, further supporting clinical evaluation of this orally efficacious budesonide therapeutic.

Abstract Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.

Abstract Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous estimation of BUD epimers in the presence of AZL with excellent efficiency in a relatively short chromatographic run (

Eosinophilic Esophagitis is an antigen-mediated inflammatory disease characterized by thickening of the esophageal wall, leading to dysphagia, vomiting, reflux, and abdominal pain. This disease can be treated with a therapeutic approach ranging from diet to pharmacological therapy. Jorveza® (budesonide) and Dupixent® (dupilumab) are treatments for Eosinophilic Esophagitis approved by the European Medicines Agency in adults but not in children. Budesonide-based extemporaneous oral liquid suspensions could be prepared for pediatric use. The main limit of this formulation is that budesonide needs a longer residence time on the esophageal mucosa to solubilize and diffuse in it to exert its local anti-inflammatory effect. Herein, we propose the development of an extemporaneous mucoadhesive oral budesonide solution for the pediatric population. A liquid vehicle containing hydroxypropyl-beta-cyclodextrin as a complexing agent and carboxymethylcellulose sodium as a mucoadhesive excipient was used to prepare budesonide-based formulations. A stable solution at a concentration of 0.7 mg/mL was successfully prepared and characterized. The formulation showed rheological and mucoadhesive properties suitable for an Eosinophilic Esophagitis local prolonged treatment. In this way, pharmacists can prepare stable budesonide-based mucoadhesive solutions, providing both patients and physicians with a new therapeutic option for Eosinophilic Esophagitis pediatric treatment.

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic “skin” CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis (“early intervention”) became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma (“anti-inflammatory reliever”, AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines.

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant’s lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide—enriched Curosurf®.

AIM: To compare the effect of different courses of budesonide nasal spray on the postoperative efficacy of endoscopic dacryocystorhinostomy.METHOD: Prospective study. A total of 90 patients(90 eyes)with chronic dacryocystitis who underwent endoscopic dacryocystorhinostomy in our hospital from January 2019 to April 2022 were selected, and they were randomly divided into three groups. In group A, 30 patients(30 eyes)continued to use budesonide nasal spray for 2mo after surgery; in group B, 30 patients(30 eyes)continued to use budesonide nasal spray for 3mo after surgery; in group C, 30 patients(30 eyes)continued to use budesonide nasal spray for 4mo after surgery. Follow-up for 6mo after surgery, Lund-Kenndey score, surgical efficacy and complications of the three groups were compared.RESULT: At 3, 4 and 6mo after surgery, the Lund-Kenndey score of group C was lower than that of group A(P0.05). Following up to 6mo, the surgical efficacy of group C was better than that of group A, and the incidence of complications was lower than that of group A(P0.05).CONCLUSION: Budesonide combined with endoscopic dacryocystorhinostomy has acceptable efficacy in the treatment of chronic dacryocystitis. After 3mo of treatment, inflammation can be well controlled, which can reduce the occurrence of postoperative complications and improve the effective rate of surgery. However, increasing the treatment course cannot further improve the effective rate of surgery.

Childhood pneumonia, often caused by acute upper respiratory tract infections or bronchitis, is one of the leading causes of mortality in children. Nebulized inhalation, as a low-risk treatment method, has garnered significant attention. However, its effectiveness and safety remain controversial. In this study, a systematic review of relevant literature on the use of budesonide (BUD) and ambroxol hydrochloride (AMB) inhalation in the treatment of childhood pneumonia was conducted, and a total of 10 articles were included. The meta-analysis revealed an odds ratio (OR) of 1.61 and an I2 value of 0.00 % for the effectiveness of combined BUD and AMB inhalation therapy in children with pneumonia, indicating no heterogeneity among the studies in terms of effectiveness. The OR values for BUD or AMB inhalation in alleviating cough, lung auscultation abnormalities, respiratory distress, body temperature, and cyanosis of the lips in children with pneumonia all favored the combined BUD therapy, showing significant relief of the aforementioned symptoms. However, due to variations in drug dosage and administration methods, high heterogeneity was observed. This study suggested that combined BUD and AMB inhalation therapy has better efficacy in treating childhood pneumonia, and BUD combined with AMB inhalation is more effective in alleviating symptoms such as cough, lung auscultation abnormalities, respiratory distress, normalizing body temperature, and reducing cyanosis of the lips. Nevertheless, further validation is required due to the limited sample size and substantial heterogeneity in the included studies. To sum up, this study provides the first analysis of the efficacy and inflammatory response of BUD and AMB inhalation in children with pneumonia. Future research should aim to verify and clarify these findings, considering the limitations of the existing studies in terms of sample size and heterogeneity.

Background and aims: Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is sometimes recommended in severe, non-responsive cases, although clinical trials have been inconclusive, raising concerns about potential complications. This study aims to investigate the effect of budesonide and mesalamine in the treatment of CDI in a murine model, by evaluating the combination of fidaxomicin and these anti-inflammatory drugs. Method: C57BL/6 J female mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or culture media by gavage. After the challenge, mice received placebo, fidaxomicin alone (20 mg/kg), or fidaxomicin combined with mesalamine (200, 400 mg/kg) or budesonide (0.2, 1, 10 mg/kg) for 5 days. The mice were monitored for 7 days with weight and survival. Colon and cecum tissues were harvested for histological assessment. Results: CDI of mice caused 80% mortality. Fidaxomicin completely protected against CDI in all parameters (weight, survival and pathscores). Mortality rates were up to 90%, 70% in budesonide(10 mg/kg) and mesalamine (400 mg/kg) treatment group, respectively. Budesonide (0.02,0.1 and 1 mg/kg) adjunction to fidaxomicin worsened the disease outcome according to all tested parameters. While mesalamine in combination with fidaxomicin (200, 400 mg/kg) did not lead to any deaths during CDI treatment, it did not provide additional benefits. Conclusions: Anti-inflammatory drugs including corticosteroid therapy may worsen the incidence and severity of CDI in this mouse model. These studies may have important clinical implications for understanding the role of anti-inflammatory/ corticosteroid therapy in CDI and inflammatory bowel disease management.

Objective Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated inflammatory oesophageal disease. Although Budesonide is recommended as one of the first-line drugs for EoE treatment, its efficacy is still controversial in multiple studies. Due to the continuous emergence of new and reliable research evidence in recent years, we updated the meta-analysis using RCT trial results to evaluate the efficacy and safety of budesonide.Materials and method Retrieve the data of the randomised controlled trial literature from 2000 to June 20, 2021, on using Budesonide in the treatment of eosinophilic esophagitis from the three major databases. Based on the results achieved with the Cochrane risk assessment tool, evaluate the quality of the included literature to extract the data, and perform the Meta-analysis with RevMan5.4 and Stata15.0.Results A total of 958 articles were retrieved, with 10 articles finally included, thus forming a sample size of 712 cases. The main outcome indicators of the meta-analysis are as follows: (1) Histological remission: the Budesonide group performs better than the placebo control group when it comes to histological remission of injuries [RR = 23.82, 95%CI = (13.46, 42.21), p

The cyclic voltammetry method was preliminarily used to study the reversibility nature of the electrochemical behaviour of budesonide (BDN) compound. The square wave-adsorptive stripping voltammetry (SW-AdSV) technique was applied to evaluate an electrochemical reduction of BDN in the phosphate buffer pH 2.5. The ultra-trace graphite working electrode was used to accumulate BDN onto its surface. An SW-AdSV reduction peak was observed in the potential of −0.98 V using Ag/AgCl reference electrode and Pt auxiliary electrode. Different parameters ,such as pH, buffer solutions, accumulations time and potential, frequency, amplitude and scan were investigated, and convection rates parameters were studied to acquire a high reduction response. The repeatability, stability, recovery, calibration curve and limit of detection and quantification parameters were studied to evaluate the analytical performance of the SW-AdSV technique. Repeatability and stability were monitored for 20 µM of BDN to give a 0.29% relative standard deviation (RSD%) that was achieved for five measurements and a very stable current for 120 min. The linearity was evaluated by studying the calibration curve over the range of 2 –25 µM (n = 8), given a linear relation between BDN concentrations and SW-AdSV signals. The limits of detection (LOD) and quantification (LOQ) were calculated to become 40 nM (0.017 ppm) and 0.134 µM (0.0577 ppm), respectively. The developed and validated method was successfully applied to the electrochemical study of BDN in pharmaceuticals and biological fluids.

Abstract Background Neutrophil infiltration accelerates the inflammatory response and is highly correlated to the development of acute lung injury (ALI). Budesonide (BUD) and N-acetylcysteine (NAC) both inhibit the inflammatory response to alleviate ALI, so we further investigated whether their combination is better for ALI. Methods In this study, we investigated the effect and mechanism of Combined BUD and NAC therapy on LPS-induced ALI. Rat ALI model and neutrophil abnormal activation model were established by lipopolysaccharide (LPS). BUD and NAC were treated alone or in combination, or cells were transfected with miR-196b-5p mimic or si-Socs3 to evaluate the efficacy and mechanism of BUD and NAC alone or in combination. Histopathological observation of lungs was performed by Hematoxylin Eosin (HE) staining. The quantity of neutrophils and inflammatory factors level in bronchoalveolar lavage fluid (BALF) were determined by Richter-Gimza complex stain and Enzyme-Linked Immunosorbnent Assay (ELISA), respectively. ReverseTranscription-PolymeraseChainReaction (RT–qPCR) was utilized to assess miR-196b-5p and inflammatory factor mRNA levels. The expression level of Socs3 was detected by immunohistochemistry or Western Blot. Results BUD and NAC combined treatment had a better effect on neutrophil recruitment and inflammatory response in LPS-induced ALI than did BUD and NAC alone. Transfection of the miR-196b-5p mimic reversed the effect of combined BUD and NAC. In conclusion, the combination of BUD and NAC is a better treatment for ALI. Conclusions Combination therapy with BUD and NAC ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis.

Immunoglobulin A nephropathy is the most common kind of primary glomerulonephritis worldwide and one of the main causes of renal failure. Systemic corticosteroid therapy may protect against renal deterioration in IgA nephropathy; however, it is not often advised for long-term treatment due to possible side effects. Recent studies present promising results of the new targeted-release formulation of budesonide that delivers the drug to the distal ileum to reduce side effects for patients with IgA nephropathy. In this paper, we highlighted the potential benefits of budesonide as a treatment option for IgA nephropathy and the need for additional studies to confirm its effectiveness. The lack of alternative treatments to prevent renal deterioration without other systemic side effects motivated us to gather relevant information to fill this gap. In this brief overview, we have reviewed some of the most recently published studies regarding how budesonide protects against IgA nephropathy. Studies reveal that budesonide might significantly decrease proteinuria, hematuria, and creatinine level while maintaining normal renal function. Though, a limited number of trials have been established to date, and further investigations are needed to confirm the benefit of the new targeted-release budesonide in treating IgA nephropathy.

Budesonide is a mineral corticoid applied in the local therapy of pediatric atopic dermatitis. Unfortunately, its dermal administration is hindered by the concomitant adverse effects and its physicochemical properties. The characteristic pH change in the atopic lesions can be utilized for the preparation of a pH-sensitive nanocarrier. In this view, the formulation of Eudragit L 100 nanoparticles as a budesonide delivery platform could provide more efficient release to the desired site, improve its penetration, and subsequently lower the undesired effects. In this study, budesonide-loaded Eudragit L100 nanoparticles were prepared via the nanoprecipitation method (mean diameter 57 nm, −31.2 mV, and approx. 90% encapsulation efficiency). Their safety was proven by cytotoxicity assays on the HaCaT keratinocyte cell line. Further, the drug-loaded nanoparticles were incorporated into two types of hydrogels based on methylcellulose or Pluronic F127. The formulated hydrogels were characterized with respect to their pH, occlusion, rheology, penetration, spreadability, and drug release. In conclusion, the developed hydrogels containing budesonide-loaded nanoparticles showed promising potential for the pediatric treatment of atopic dermatitis.

Agglomerate formulations for dry powder inhalation (DPI) formed with fine particles are versatile means for the highly efficient delivery of budesonide. However, uncontrolled agglomeration induces high deposition in the upper airway, causing local side effects due to high mechanical strength, worse deagglomeration, and poor fine-particle delivery. In the present study, fine lactose was mechanically dry-coated prior to particle agglomeration, and the agglomerates were then spheroidized via ultrasonic vibration to improve their aerosol performance. The results showed that the agglomerate produced with the surface-enriched hydrophobic magnesium stearate and ultrasonic vibration demonstrated improved aerosolization properties, benefiting from their lower mechanical strength, less interactive cohesive force, and improved fine powder dispersion behavior. After dispersion utilizing a Turbuhaler® with a pharmaceutical cascade impactor test, a fine particle fraction (FPF) of 71.1 ± 1.3% and an artificial throat deposition of 19.3 ± 0.4% were achieved, suggesting the potential to improve the therapeutic outcomes of budesonide with less localized infections of the mouth and pharynx.

Introduction: Epidermolysis bullosa is a genetic condition with skin fragility that leads to blister formation and erosion following minor trauma. This disease also involves the gastrointestinal tract by way of esophageal stricture and dysphasia. Some studies have recommended oral budesonide liquid therapy to decrease the need for balloon endoscopy and other aggressive treatments. The aim of the study was to evaluated clinical symptoms of patients who consumed oral budesonide in their daily routine therapies. Methods: This cross-sectional study was conducted in Akbar Hospital of the Mashhad University of Medical Sciences. All enrolled patients were followed between July and October 2021. Ten milliliter oral budesonide (0.5 milligram) liquid was administrated one hour before eating. They were followed up to determine and document any side effects after treatment, and any improvement of clinical symptoms such as amelioration of dysphasia, volume of food intake, duration of food consumption, and kind of food consumed (solid versus liquid).Results: About fifteen patients were studied. The mean duration + SD of using budesonide was 9.66±15.76 weeks. The mean percentage + SD was 41.33±34.61 for improvement in the volume of food intake, and the mean for improving dysphasia + SD was 42±33.63%. Three patients suffered from complications (i.e., mucositis and gastric fullness). Also, two patients did not want to continue treatment because they did not like the drug taste.Conclusion: Oral budesonide liquid could be recommended for epidermolysis bollusa patients to improve clinical symptoms.

Abstract Background Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis. Objective To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution. Methods Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Recently, there have been multiple advances in the understanding of IgAN pathophysiology and therapeutic options. Despite the advent of new treatment options, individual risk stratification of the disease course and choosing the best treatment strategy for the patient remains challenging. A multitude of clinical trials is ongoing, opening multiple opportunities for enrollment. In this brief review we discuss the current approach to the management of IgAN and highlight the ongoing clinical trials.

Purpose: Postoperative sore throat (POST) is a common complication. We compared postoperative nebulized furosemide, budesonide, and sodium chloride solution for POST in patients undergoing maxillofacial surgery. Methods: 75 patients were randomly divided into 3 groups. Anesthesia induction and intubation were routinely performed. Following emergence, the patients were randomized to one of three groups. Group F was treated with 40mg of aerosolized furosemide, group B received 2 mg of aerosolized budesonide and Group S was given aerosolized 0.9% sodium chloride solution. Patients were assessed for sore throat,hoarseness, foreign body sensation,dry mouth, cough，nausea and vomiting at 15 min, 1, 2, 4, 6, 8, 12, 24 and 48 h after extubation. Results: Patients all in three groups had comparable clinical and surgical data.Compared to Group S, POST at rest and during swallowing was significantly lower in Group F and Group B at 2, 4, 6, 8 and 12 h (P

Introduction: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn’s disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. Methods: In this phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn’s disease with a Crohn’s disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. Results: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and

Background and aim Meconium-aspiration syndrome (MAS) is a common cause of respiratory distress. MAS is a serious disease that affects neonates born through meconium-stained amniotic fluid. The pathophysiology of MAS is multifactorial, inflammation has an important role in MAS, so anti-inflammatory drugs like corticosteroids may be effective in the treatment of MAS. Budesonide is a nonhalogenated glucocorticoid that can reduce vascular permeability, inhibit secretion of mucus, relieve edema and spasm, and help pulmonary ventilation. In this study we aimed to find out the effect of early nebulized budesonide in the treatment of MAS. Patients and methods This was a prospective study conducted during the period from October 2017 to July 2018 at El-Minia General Hospital and Al-Azhar University Hospital, Assiut. Intervention: budesonide inhalation in a dose of 50 mg every 12 h till clinical recovery, whichever was earlier. Results The present study revealed that nebulized budesonide improves the clinical outcome of newborns with MAS in terms of lowering the duration of O2 dependency, duration of respiratory distress, duration of hospital stay, duration of radiograph clearance, time for full feeding (P

Immunoglobulin A (IgA) nephropathy is a common autoimmune kidney disease. Accumulating studies showed that IgA nephropathy may be partially correlated with mucosal immune system dysfunction. Systemic corticosteroid treatment exerts an essential protective effect against renal deterioration in IgA nephropathy. However, long-term use of corticosteroids may cause systemic side effects. The novel targeted-release formulation (TRF) of budesonide has been shown to deliver the drug to the distal ileum with the aim of minimizing adverse events for patients with IgA nephropathy. In this review, we have summarized all the current evidence of the effects of TRF-budesonide protecting against IgA nephropathy. Three randomized controlled trials (RCTs), one cohort, two case reports, and an ongoing Phase 3 trial (Part B, NCT03643965), were under comprehensive review. These included studies demonstrated that TRF-budesonide could remarkably reduce proteinuria, hematuria, and creatinine, as well as preserve renal function. The local immunosuppressive effects exhibited by TRF-budesonide may represent a novel and promising approach to treating IgA nephropathy. However, the current evidence was only derived from limited trials. Therefore, more well-designed RCTs are still warranted to validate the curable profile of TRF-budesonide in treating IgA nephropathy.

IntroductionCollagenous colitis (CC) is an inflammatory bowel disease, which usually responds to budesonide treatment. Our aim was to study the immunological background of the disease.MethodsAnalyses of peripheral and mucosal MAIT (mucosa associated invariant T cells) and NK (natural killer) cells were performed with flow cytometry. Numbers of mucosal cells were calculated using immunohistochemistry. We studied the same patients with active untreated CC (au-CC) and again while in remission on budesonide treatment. Budesonide refractory patients and healthy controls were also included. The memory marker CD45R0 and activation marker CD154 and CD69 were used to further study the cells. Finally B cells, CD4+ and CD8+ T cells were also analysed.ResultsThe percentages of circulating CD56dimCD16+ NK cells as well as MAIT cells (CD3+TCRVa7.2+CD161+) were decreased in au-CC compared to healthy controls. This difference was not seen in the mucosa; where we instead found increased numbers of mucosal CD4+ T cells and CD8+ T cells in au-CC. Mucosal immune cell numbers were not affected by budesonide treatment. In refractory CC we found increased mucosal numbers of MAIT cells, CD4+ and CD8+ T cells compared to au-CC.DiscussionPatients with active collagenous colitis have lower percentages of circulating MAIT and NK cells. However, there was no change of these cells in the colonic mucosa. Most mucosal cell populations were increased in budesonide refractory as compared to au-CC patients, particularly the number of MAIT cells. This may indicate that T cell targeting therapy could be an alternative in budesonide refractory CC.

The gut microbiome is essential for maintaining organismal health. Gut microbiota may be disrupted through external factors like dietary change, which can lead to gut inflammation, resulting in obesity. Hibernating mammals develop low-grade gut inflammation when they accumulate fat deposits in preparation for hibernation, making them useful models for studying the relationship between the microbiome, inflammation, and weight gain. Nonsteroidal anti-inflammatory drugs and steroids are commonly used in humans to target gut inflammation, but how these drugs affect the gut microbiome and its stability is unclear. We investigated the effect of the glucocorticoid drug budesonide on the gut microbiome and cytokine levels of an obligate hibernator, the 13-lined ground squirrel, during the fattening season. We used 16S rRNA gene sequencing to characterize bacterial communities in the lumen and mucosa of the cecum and colon and measured proinflammatory [tumor necrosis factor-α (TNF-α)/interleukin 6 (IL-6)] and anti-inflammatory (IL-10) cytokine levels. Budesonide affected the microbiome only in the cecum lumen, where bacterial diversity was higher in the control group, and communities significantly differed between treatments. Across gut sections, Marvinbryantia and Enterococcus were significantly higher in the budesonide group, whereas Sarcina was higher in the control group. TNF-α and IL-6 levels were higher in control squirrels compared with the budesonide group, but there was no difference in IL-10 levels. Overall, budesonide treatment affected the microbial community and diversity of 13-lined ground squirrels in the cecum lumen. Our study presents another step toward developing ground squirrels as a model for studying the interaction between the microbiota and host inflammation. NEW & NOTEWORTHY Disruptions of gut microbiota can lead to inflammation, resulting in weight gain. Inflammation can be treated with budesonide, but how budesonide affects gut microbiota is unclear. Thirteen-lined ground squirrels experience low-grade gut inflammation during prehibernation fattening, which compares with human inflammation-weight gain mechanisms. We showed that budesonide treatment decreased microbiome diversity and lead to a shift in community in the cecum lumen. Our study supports developing ground squirrels as a model for studying microbiome-inflammation interactions.

Background/objectives: Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE., Methods: This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties., Results: A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties., Conclusions: This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Background: An orodispersible form of budesonide has recently been approved for the targeted treatment of eosinophilic oesophagitis in the United Kingdom, Europe, Australia, Canada and the United States, following favourable results from a randomised controlled trial. This is the first dedicated real-world study exploring the safety and efficacy of budesonide orodispersible tablets for induction therapy in the treatment of eosinophilic oesophagitis while providing insights into its management., Objectives: The primary objective was histologic remission, defined as less than 5 eosinophils per high-powered field. The secondary objectives included histologic response (>50% reduction in peak eosinophil count), clinical remission (complete resolution of symptoms documented on clinic letters), clinical response (improvements in symptoms as reported on clinical letters), endoscopic remission (Endoscopic Reference Score (EREFS) score = 0), and endoscopic response (improvement in EREFS score). The EREFS scores were calculated based on the severity and presence of rings, longitudinal furrows, strictures, oedema and exudates on endoscopic images. Adverse events and safety profiles were also recorded., Design: A multicentre cohort study examining the effectiveness of 1 mg, twice daily, budesonide orodispersible tablet induction therapy for the treatment of eosinophilic oesophagitis., Methods: Ethics approval was obtained through the Western Australia Health: Governance, Evidence, Knowledge, Outcomes system for assessment of Audit and Quality Activities. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines., Results: A total of 43 patients (29 males, 14 females; median age 39) were recruited. Forty-one patients were included in the analysis. After induction therapy, 30 patients (73%) achieved histologic remission, and 35 patients (85%) demonstrated histologic response. Thirty-nine patients (95%) achieved clinical response, and 28 patients (68%) achieved clinical remission. An endoscopic response was seen in 37 patients (90%), and 16 patients (39%) achieved endoscopic remission. No significant adverse events were identified., Conclusion: Budesonide orodispersible tablet is an effective induction therapy for eosinophilic oesophagitis, as evidenced by its high histologic remission rate and favourable safety profile., Competing Interests: Dr. Sherman Picardo has served as a speaker/consultant for Abbie, Falk, Janssen Pfizer and Takeda., (© The Author(s), 2024.)

Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s., Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018., Design: Retrospective observational study., Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD ( n  = 386) at our clinic for those diagnosed between 2006 and 2018., Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1-5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = -0.164, p  = 001), but had increased for budesonide (rs = 0.202, p  < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p  = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p  = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = -201, p  = 0.012)., Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Neonatal acute respiratory distress syndrome (NARDS) is an important cause of hypoxemic respiratory failure. This study aimed to investigate the short-term effects of endotracheal surfactant and budesonide combination therapy on NARDS secondary to late-onset neonatal sepsis (LONS)., Methods: This was a retrospective, cross-sectional, and observational study. Newborns with NARDS due to LONS who received endotracheal surfactant and budesonide combination therapy between August 2022 and September 2023 were included in this study. Oxygenation status before endotracheal surfactant and budesonide treatment were compared with the values obtained two hours after treatment., Results: Among 20 neonates, 10 (50%) were diagnosed with severe NARDS, and 10 (50%) were diagnosed with moderate NARDS. The mean corrected gestational age was 33.3±2.9 w when endotracheal surfactant and budesonide were administered to the neonates. The need for the fraction of inspired oxygen (0.75 [0.57-1.00]% vs. 0.55 [0.44-0.80]%; mean difference [MD]: 17.50%, 95% confidence interval [CI]: 14.99 to 22.50) and oxygen saturation index (OSI; 8.03 [4.98-13.94] vs. 4.71 [4.11-8.93]; MD: 2.23, 95% CI: 1.22 to 3.24) decreased ( P =0.001 and P <0.001, respectively) after endotracheal surfactant and budesonide treatment. However, preductal oxygen saturation (SpO 2 ; 93 [91-94]% vs. 95 [94-96]%; MD: -3.50%, 95% CI: -5.00 to -2.00) increased significantly after endotracheal surfactant and budesonide treatment when compared to pre-treatment values ( P <0.001)., Conclusion: The reduction in oxygen demand and OSI, along with an increase in SpO 2 after treatment compared to pre-treatment values, suggests that endotracheal surfactant and budesonide combination therapy could be an effective option to improve oxygenation in NARDS secondary to LONS., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

This study aimed to establish a feasible dissolution method for inhalation aerosols. A method of collecting fine particles was investigated to capture aerosol particles less than 4 μm in diameter for dissolution tests. This dose collection method enabled the aerosol particles to be uniformly distributed on the glass fiber filter, thus considerably reducing particle agglomeration. Budesonide was used as a model drug. The aerodynamic particle size distribution (APSD) of the meter-dose inhaler (MDI) was compared by replacing actuators with different orifice sizes. Dissolution tests were conducted on fine particle doses collected using various actuators, and the dissolution profiles were modeled. The fine particle dose decreased with an increasing orifice size of the actuator. Actuators with different orifice sizes would affect the dissolution behavior of inhaled drugs. This finding was supported by similarity factor f 2 analysis, suggesting the dissolution method has a discriminative capacity. The results of various model fits showed that the dissolution profiles produced by the different actuators could be fitted well using the Weibull mathematical model. The method employed in this study could offer a potential avenue for exploring the relationship between the orifice size of the actuator and the dissolution behavior of inhaled corticosteroids. This dissolution method was simple, reproducible, and suitable for determining the dissolution of inhalation aerosols., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear., Objective: To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC., Methods: We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables., Results: A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3 years (interquartile range (IQR) = 50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI = 1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI = 1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases., Conclusion: Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

This study aimed to investigate the amorphous stabilization of BCS Class II drugs using mesoporous silica as a carrier to produce amorphous solid dispersions. Ibuprofen, fenofibrate, and budesonide were selected as model drugs to evaluate the impact of molecular weight and partition coefficient on the solid state of drug-loaded mesoporous silica (MS) particles. The model drugs were loaded into three grades of MS, SYLYSIA SY730, SYLYSIA SY430, and SYLYSIA SY350, with pore diameters of 2.5 nm, 17 nm, and 21 nm, respectively, at 1:1, 2:1, and 3:1, carrier to drug ratios, and three different loading concentrations using solvent immersion and spray drying techniques. Differential scanning calorimetry (DSC) thermograms of SY430 and SY350 samples exhibited melting point depressions indicating constricted crystallization inside the pores, whereas SY730 samples with melting points matching the pure API may be a result of surface crystallization. Powder x-ray diffraction (PXRD) diffractograms showed all crystalline samples matched the diffraction patterns of the pure API indicating no polymorphic transitions and all 3:1 ratio samples exhibited amorphous halo profiles. Response surface regression analysis and Classification and Regression Tree (CART) analysis suggest carrier to drug ratios, followed by molecular weight, have the most significant impact on the crystallinity of a drug loaded into MS particles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Budesonide (BDS) a steroid-based anti-inflammatory drug widely prescribed for various diseases, has a low aqueous solubility. In this study, we investigated cosolvency approach to study the thermodynamic specifications related to the solubility of BDS at the temperature range of 293.2-313.2 K in (1-propanol + water) mixtures applying the shaking flask method. The predictive power of different mathematical models for experimental data in the cosolvency systems was evaluated. For this purpose, the linear and nonlinear mathematical equations such as van't Hoff model (as a linear model), Buchowski-Ksiazczak equation (as a non-linear), CNIBS/R-K and MRS models (as a linear model for solvent composition at an isothermal condition), modified Wilson model (as a non-linear model for isothermal condition), the Jouyban-Acree model (as a model that considers temperature and solvent composition), and Jouyban-Acree-van't Hoff model (as a model with no further input data) were studied. Also, the Williams-Amidon excess Gibbs energy model was investigated. In addition, the related apparent thermodynamics of the BDS dissolution process in the desired temperature such as Gibbs free energy, enthalpy, and entropy, were computed by the corresponding equations. Moreover, based on the inverse Kirkwood-Buff integrals, it is demonstrated that BDS is preferentially solvated by water in water-rich mixtures. The accuracy of the fitness was evaluated with mean relative deviations (MRDs%) for back-calculated molar BDS solubility data. The result showed that the maximum solubility of BDS was obtained at 0.7 mass fraction of 1-propanol at all temperatures. Thermodynamic studies demonstrated that BDS dissolution procedures were obtained as endothermic and entropy-driven in almost all cases. The overall MRDs% values for the back-computed BDS solubility in the aqueous mixture of 1-propanol based on van't Hoff model, Buchowski-Ksiazczak equation, CNIBS/R-K model, modified Wilson model, Jouyban-Acree model, Jouyban-Acree-van't Hoff model, MRS model, and Williams-Amidon excess Gibbs energy model were found 1.93%, 1.80%, 11.68%, 33.32%, 12.30%, 9.24%, 10.70%, and 6.57%, respectively., (© 2024. The Author(s).)

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that is immune/antigen-mediated and often requires targeted treatment. In clinical practice, an oral viscous budesonide suspension prepared by adding sucralose to a budesonide suspension for inhalation (Pulmicort®) is used to treat adult EoE and enhance retention in the esophageal mucosa. Inspired by this off-label drug use, oral viscous budesonide solutions (OVBSs) were developed in this study, and their capacities for adhesion, permeation, and stability were explored. Given the insolubility of budesonide as a BCS II drug, we first evaluated its equilibrium solubility and found that Transcutol® HP was an excellent choice for creating an OVBS at a concentration of 0.2 mg/g. The rheological properties of the OVBSs were evaluated with a rheometer, and shear-thinning, which aids in swallowing, was observed. The addition of hydroxyethyl cellulose (HEC) increased the adhesion strength of the preparation, which was associated with the hydration and thickening mechanism. This result was confirmed in a dynamic gelation study and in vitro elution experiment conducted with porcine esophagus tissue. Furthermore, the permeabilities of the OVBSs in the porcine esophagus were evaluated with a Franz diffusion cell device. >80 % of the budesonide was released after 24 h, and the release profile was similar to that of the solution. To explore the storage conditions of OVBSs, critical factors such as pH, content, and impurities were determined. It was found that OVBSs exhibited different behaviors at different pH values and temperatures. Notably, the OVBSs containing 1.7 % HEC could be stored for >6 months at a temperature of 5 °C ± 3 °C and a pH of 4.5 without significant degradation. Overall, this study demonstrated that OVBSs have the potential to adhere to the esophageal mucosa, permeate the tissue, and remain stable during storage. Moreover, OVBSs exhibit a distinct advantage over traditional converted inhalation-to-oral budesonide therapies by enabling flexible dose adjustment in clinical applications, thereby potentially minimizing systemic side effects commonly associated with oral glucocorticoid administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)