Budesonide Research Articles

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-β contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

CT-207 Protracted Diarrhea from High-Dose Melphalan in Autologous Hematopoietic Transplantation: Response to Short Course of Oral Budesonide

Approximately, 40% of patients receiving high dose melphalan (HDM) develop grade III or IV diarrhea (CTCAE 5.0) that promptly improves upon neutrophilic engraftment. Persistence of grade III diarrhea beyond 72 hours post-engraftment, though uncommon results in significant morbidity and prolongs hospitalization. Enlighten by a histopathologic finding of crypt inflammation, we utilized a short course of oral budesonide in a patient resulting in rapid resolution of diarrhea. We herein document 3 such cases and discuss their role in reducing morbidity and duration of hospitalization. All patients (age 44, 63 and 65, 2 female) received melphalan 200 mg/m2. Neutrophilic engraftment occurred on day +11 in 2 patients and day +12 in 1. Persistent grade III diarrhea 72 hours after neutrophil engraftment is defined as protracted diarrhea from melphalan. Infectious workup included stool examination for salmonella, shigella, rotavirus, cryptosporidium, and clostridium difficile we negative. Colonoscopy in one patient confirmed patchy crypt apoptosis and crypt abscess formation. Standard supportive care including antidiarrheals offered no improvement. Oral budesonide (BUD)was introduced at 5, 7- and 16-days post-engraftment (day + 17, +18 and +27 of ASCT). The dose of BUD comprised 6 mg/day in 2 while one patient received a 9 mg/day dose. Two patients had rapid resolution of diarrhea within 48 hours, while the third patient improved in 7 days. Total duration of BUD was 2, 2, and 26 days. Patients received a total cumulative dose of 12 mg, 15 mg, and 117 mg. Time to discharge from BUD initiation was 2, 2, and 7 days. A translational model of melphalan-induced gut toxicity reveals drug-host-microbe interaction that drives tissue injury and inflammation. Palifermin, a recombinant human keratinocyte growth factor is effective in reducing diarrhea of HDM. However, its cost is prohibitive. While newer melphalan preparations are available and prevention of melphalan-induced GI toxicity is being studied (Uproleselan), a short course of oral budesonide provided rapid resolution and facilitated patient discharge. Oral BUD results in rapid resolution of lower GI toxicity of HDM and potentially lowers the cost of hospitalization.

Green microemulsion electrokinetic chromatographic method for simultaneous determination of azelastine and budesonide

A facile, sensitive, and eco-friendly microemulsion electrokinetic chromatographic method coupled with field amplified sample stacking was developed for the simultaneous determination of azelastine (AZL) and budesonide (BUD) in their combined pharmaceutical preparations. The separation of both drugs was achieved using 13 mM borate buffer (pH 9.0) containing 1.2% sodium dodecyl sulphate (SDS), 2.4% n-butanol, and 1.0% ethyl acetate as the background electrolyte (BGE). A capillary tube (40 cm effective length; 75 μm internal diameter) of uncoated fused silica was used for separation of the studied analytes. A diode array detector was used to monitor the studied compounds at 195 nm. The applied voltage and temperature were adjusted at 28 kV and 25 °C, respectively. The method was linear over the concentration ranges of 0.5–50.0 μg/mL for azelastine and 1.0–20.0 μg/mL for budesonide. The sensitivity was improved by more than 10 folds by using field amplified sample stacking technique. Moreover, the method was applied for separation of budesonide epimers (22R-BUD and 22S-BUD) by increasing the concentration of SDS in the BGE to be 1.8%. Greenness evaluation was performed using analytical eco-scale, Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE) approaches. The excellent green profile of the developed method, confirmed by the three approaches, has supported its applicability in quality control laboratories.

Efficacy of combined nebulized aerosol inhalation and pulmicort respules in the treatment of emergency pediatric laryngitis, and its effect on adverse reactions

Purpose: To determine the efficacy of combined use of nebulized epinephrine inhalation and pulmicortrespules in the treatment of emergency pediatric laryngitis and, its impact on the incidence of adverse reactions.Methods: A total of 100 cases of pediatric laryngitis admitted in The People’s Hospital of Zhangqiu District between December 2018 and December 2020 were randomly assigned (1:1) to receive either pulmicort respules (control group) or pulmicort respules plus nebulized epinephrine inhalation treatment (study group). Outcome measures included level of effectiveness and adverse reactions.Results: Pulmicort respules plus nebulized epinephrine inhalation treatment was associated with shorter remission time for dyspnea, wheeze, croup, and hoarseness versus pulmicort respules. The combination treatment produced higher total effectiveness of 96 % than pulmicort respules with total effectiveness of 82 % (p < 0.05). After treatment, both groups had decreased serum levels of interleukin-8 (IL-8), IL-6, C-reactive protein (CRP), and tumor necrosis factor (TNF)-α, with markedly lower levels in the group given nebulized epinephrine inhalation in combination with pulmicort respules (p < 0.05). Compared with patients given pulmicort respules only, those given combination treatments had a significantly shorter hospitalization time and a lower incidence of adverse reactions (4 vs 8 %; p < 0.05).Conclusion: Nebulized epinephrine inhalation in combination with pulmicort respules has high safety in the treatment of emergency pediatric laryngitis, and it significantly reduces clinical symptoms, inflammatory response, and hospital stay. However, further clinical trials are required prior to its use in clinical practice.

Comparing the Efficacy and Safety Profile of Triple Fixed-Dose Combinations in COPD: A Meta-Analysis and IBiS Score.

Background: Triple fixed-dose combination (FDC) therapy is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations and/or symptoms not controlled by dual FDCs. Since no randomized controlled trials (RCTs) have directly compared the different inhaled corticosteroid/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) FDCs, we performed a meta-analysis to compare the impact of the current available ICS/LABA/LAMA FDCs in COPD. Methods: A meta-analysis was performed by connecting beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide or glycopyrrolate (BDP/FOR/GLY), budesonide (BUD)/GLY/FOR, and fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) FDCs via ICS/LABA or LABA/LAMA FDCs arms. The safety and efficacy profiles were investigated, and the Implemented Bidimensional Surface under the cumulative ranking curve analysis (IBiS) was carried out. Protocol registration: CRD42022301189. Results: Data from 21,809 COPD patients were extracted from the ETHOS, IMPACT, KRONOS, and TRILOGY studies. No significant (p > 0.05) differences were detected across the triple FDCs with respect to the risk of exacerbation, trough forced expiratory volume in the first second (FEV1), transition dyspnea index (TDI), St. George’s Respiratory Questionnaire (SGRQ), risk of serious adverse events (SAEs), cardiovascular (CV) SAEs, pneumonia, and all-cause mortality. According to IBiS score, BDP/FOR/GLY 200/12/25 µg twice daily (BID) was the FDC reporting the best combined efficacy/safety profile (area 41.41%), although FF/UMEC/VI 100/62.5/25 µg once daily (QD) showed the greatest efficacy profile (50.54%). The protection against mortality related to the dose of ICS. Conclusions: All triple FDCs are effective and safe in COPD regardless of the regimen of administration (twice daily vs. once daily), with no relevant difference in the risk of CV SAEs and pneumonia.

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD.

Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.

Gold immunochromatographic strip assay for the detection of triamcinolone acetonide and budesonide in milk

A monoclonal antibody against triamcinolone acetonide (TCA) and budesonide (BUD) was prepared using a hapten that was generated by introducing a carboxyl group into the structure of TCA. Based on the prepared monoclonal antibody, a gold nanoparticle-based lateral-flow immunoassay (GLFA) was developed with the ability to screen TCA and BUD in milk. The visible limits of detection of the GLFA for the analysis of TCA and BUD were 0.1 and 0.5 ng/mL with a cutoff value of 5 and 10 ng/mL, respectively, in milk. Average recoveries of TCA and BUD in milk were 92.0–102.2% and 96.0–98.8% with a good correlation between the results from the GLFA and LC-MS/MS analysis. These results demonstrated that the GLFA method for the rapid detection of TCA and BUD in milk samples is reliable and sensitive.

A Pilot Randomized Trial of As-Needed Budesonide-Formoterol for Stepping Down Controller Treatment in Moderate Asthma with Complete Remission.

BackgroundThe use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission.MethodsWe randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 μg) twice daily to receive BFM (160/4.5 μg) as needed (16 patients), or budesonide (BUD) (200 μg) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups.ResultsSix patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44–7.12; p=0.41). The changes in forced expiratory volume in 1 second were −211.3 mL with as-needed BFM versus −97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049).ConclusionCompared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.

Square wave-adsorptive stripping voltammetric technique development and validation for the determination of budesonide in pharmaceuticals and biological fluids using graphite working electrode

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.

Pulmonary delivery of resveratrol-β-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury

Smoke bombs are often used in military/fire training, which can produce a large amount of zinc chloride (ZnCl2) smoke. Inhalation of ZnCl2 smoke usually causes acute lung injury (ALI) that would likely develop to acute respiratory distress syndrome (ARDS). However, there is no effective prevention or treatment strategy for the smoke-induced ALI. Resveratrol (RES) is a natural polyphenol with good anti-inflammatory and anti-apoptotic activities, but its low solubility, stability, and bioavailability restrict its clinical application. In this study, an inhalable RES formulation composed of RES-β-cyclodextrin inclusion complexes (RES-β-CD) was prepared for the prevention of ZnCl2 smoke-induced ALI. RES-β-CD powders had a small mass median aerodynamic diameter of 3.61 μm and a high fine particle fraction of 38.84%, suitable for pulmonary inhalation. RES-β-CD exhibited low BEAS-2B cytotoxicity. Pulmonary delivery of RES-β-CD to mice remarkably prevented the smoke-induced ALI with downregulation of TNF-α, IL-1β, STAT3, and GATA3, and upregulation of T-bet and Foxp3. RES-β-CD protected the respiratory function, percutaneous oxygen saturation, physical activity, lung capillary integrity, and lung liquid balance, alleviating inflammation and apoptosis. Pulmonary delivery of the positive drug, budesonide (BUD), also alleviated the smoke-induced ALI by reduction of inflammation and cell apoptosis. RES-β-CD exhibited the regulation of the Th1/Th2 and Treg/Th17 balances, while BUD did not show any effect on immune balances. In conclusion, pulmonary delivery of RES-β-CD is a promising anti-inflammatory and anti-apoptosis strategy for the prevention of ZnCl2 smoke-induced ALI by direct lung drug distribution and regulation of immune balance.

Suhuang Antitussive Capsule Ameliorates Corticosteroid Insensitivity in Cough Variant Asthma Guinea Pigs by Inhibiting p38 MAPK Signal Pathway.

Methods The CVA guinea pig model was successfully established by use of ovalbumin (OVA) sensitization and cigarette smoke (CS) exposure. The guinea pigs were divided into 6 groups: a control group, an OVA model group, an OVA + CS model group, a Suhuang treatment group, a BUD treatment group, and a combination (Suhuang and BUD) treatment group. The effects of the treatment were determined by measuring lung function (RI/Cydn) and cough symptoms (coughs number/cough latency) as outcome criteria. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Lung tissues were stained by hematoxylin and eosin (H&E). The expressions of GR/total p38 MAPK/p-p38 MAPK were detected by Western blot. The MKP-1 mRNA levels were detected by RT-PCR. Results Combination treatment significantly decreased RI/coughs numbers and increased Cydn/cough latency. Significantly, the results indicated that combination treatment decreased injury to pulmonary tissues. Results also revealed that levels of inflammatory cytokines were reduced in all treatment groups but most markedly in the combination treatment group. Moreover, Suhuang treatment significantly ameliorated corticosteroid insensitivity by improving the expression of glucocorticoid receptors (GR). The expressions of total p38 MAPK and p-p38 MAPK in lung tissue were significantly inhibited in the Suhuang and combination treatment groups. The MKP-1 mRNA levels in Suhuang and combination treatment groups were also increased significantly. Conclusion Suhuang was effective for reversing corticosteroid insensitivity by regulating the p38 MAPK signal pathway, and combining BUD and Suhuang treatment showed synergistic interactions in CVA guinea pigs. Our findings showed that this combination therapy might be a promising therapeutic agent for CVA and also clarified its underlying mechanism of action, providing a theoretical basis for clinical combination treatment with Suhuang and BUD in CVA patients.

New Versus Old: The Impact of Changing Patterns of Inhaled Corticosteroid Prescribing and Dosing Regimens in Asthma Management.

Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a long-acting bronchodilator, depending on asthma severity, and may also be supplemented with short-acting bronchodilators for as-needed rescue medication. Adherence to asthma therapies is generally poor and characterized by underuse of ICS therapies and over-reliance on short-acting bronchodilators, which leads to poor clinical outcomes. This article reviews efficacy versus systemic activity profiles for various dosing regimens of budesonide (BUD) and fluticasone propionate (FP). We performed a structured literature review of BUD and FP regular daily dosing, and BUD/formoterol (FOR) as-needed dosing, to explore the relationship between various dosing patterns of ICS regimens and the risk–benefit profile in terms of the extent of bronchoprotection and cortisol suppression. In addition, we explored how adherence could potentially affect the risk–benefit profile, in patients with mild, moderate, and moderate-to-severe asthma. With a specific focus on BUD or FP-containing treatments, we found that regular daily ICS and ICS/long-acting β2-agonist (LABA) dosing had a greater degree of bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR maintenance and reliever therapy (MART) dosing, and still maintained low systemic activity. We also found that the benefits of regular daily ICS dosing regimens were diminished when adherence was low (50%); the shorter duration of bronchoprotection observed was similar to that seen with typical as-needed BUD/FOR usage. These findings have implications for aiding clinicians with selecting the most suitable treatment option for asthma management, and subsequent implications for the advice clinicians give their patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02092-7.

Curcumin-Loaded mPEG-PLGA Nanoparticles Attenuates the Apoptosis and Corticosteroid Resistance Induced by Cigarette Smoke Extract.

The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin’s effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.

STABILITY INDICATING HPTLC METHOD FOR ESTIMATION OF BUDESONIDE AND FORMOTEROL FUMARATE DIHYDRATE IN PHARMACEUTICAL FORMULATION

A sensitive, selective, precise and accurate stability-indicating high-performance thin layer chromatographic method for analysis of budesonide (BUD) and formoterol fumarate dihydrate (FFD) was developed along with forced degradation study and validated according to ICH guidelines. Densitometry analysis of BUD and FFD was carried out in the absorbance mode at 234 nm using toluene: methanol: ethyl acetate: ammonia (8:2:2.5:0.1,% V/V/V/V) as solvent system. This system was found to give compact spots for BUD at Rf value of 0.34 ± 0.06 and FFD at Rf value of 0.67± 0.05. It was found that besides oxidative, thermal and photo stability studies, acid and base induced degradation of drugs were more with resultant degradation product. 32 factorial design was used to predict base induced degradation. The drug undergoes degradation under mainly acidic and basic conditions. Also, the degraded products were well resolved from the pure drugs with significantly different Rf values. Linearity was found to be in the range of 1800-10600 and 1000-6000 ng band-1 for BUD and FFD, respectively. The LOQ for BUD and FFD were 392.48 ng band-1 and 1189.36 ng band-1 and LOD for BUD and FFD was115.79 ng band-1 and 350.88 ng band-1, respectively. ‘‘Bartlett’s test’’ applied on peak area for linearity, additionally proved validity of the developed method. Good accuracy and precision were obtained as revealed from percentage RSD value less than 2. Similarly, no interference was observed from common excipients in tablet formulation as well as degradation product, indicating specificity of the method. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.

Effect of Corticosteroids on Peptide Transporter 2 Function and Induction of Innate Immune Response by Bacterial Peptides in Alveolar Epithelial Cells

In the lung alveolar region, the innate immune system serves as an important host defense system. We recently reported that peptide transporter 2 (PEPT2) has an essential role in the uptake of bacterial peptides and induction of innate immune response in alveolar epithelial cells. In this study, we aimed to clarify the effects of corticosteroids on PEPT2 function and PEPT2-dependent innate immune response. NCI-H441 (H441) cells were used as an in vitro model of human alveolar type II epithelial cells, and the effects of dexamethasone (DEX) and budesonide (BUD) on the transport function of PEPT2 and the innate immune response induced by bacterial peptides were examined. PEPT2 function, estimated by measuring β-alanyl-Nε-(7-amino-4-methyl-2-oxo-2H-1-benzopyran-3-acetyl)-L-lysine (β-Ala-Lys-AMCA) uptake in H441 cells, was suppressed by treatment with DEX and BUD in a concentration- and time-dependent manner. The suppression of PEPT2 function was partially recovered by a glucocorticoid receptor antagonist. The expression of PEPT2 and nucleotide-binding oligomerization domain 1 (NOD1) mRNAs was suppressed by treatment with DEX and BUD, while PEPT2 protein level was not changed by these treatment conditions. Additionally, the increased mRNA expression of interleukin (IL)-8 and the increased secretion of IL-8 into the culture medium induced by bacterial peptides were also suppressed by treatment with these corticosteroids. Taken together, these results clearly suggest that corticosteroids suppress PEPT2 function and bacterial peptide-induced innate immune response in alveolar epithelial cells. Therefore, PEPT2- and NOD1-dependent innate immune response induced by bacterial peptides in the lung alveolar region may be suppressed during the inhaled corticosteroid therapy.

Preparation and characterization of colon-targeted pH/Time-dependent nanoparticles using anionic and cationic polymethacrylate polymers

Inflammatory bowel disease (IBD), which is a chronic inflammatory disease of the gastrointestinal system, has two subtypes: Ulcerative Colitis (UC) and Crohn's Disease (CD). Only pH-sensitive drug delivery systems are commonly utilized for the treatment of IBD, but their effectiveness is frequently obstructed by the change in intestinal pH. To overcome the inadequacy of only pH-dependent delivery systems, we developed in vitro evaluated both pH- and time-dependent nanoparticles loaded budesonide (BUD) for the treatment of IBD in this study. Anionic polymethacrylate was utilized as a pH-dependent polymer whereas cationic polymethacrylate was utilized as a time-dependent sustained release polymer. Nanoparticles were prepared through a single oil-in-water emulsion/solvent evaporation method. The encapsulation efficiency, mean particle size, zeta potential, polydispersity index (PDI), drug release profiles, drug release kinetics, and stability of these nanoparticles were investigated. In all formulations, mean particle sizes were below 250 nm and PDI values were between 0.1 and 0.3. Nanoparticles containing 90% anionic-10% cationic polymethacrylate polymers inhibited burst BUD release under acidic conditions and exhibited sustained drug release at neutral pH. Consequently, in the medication of IBD, BUD-loaded pH and time-dependent nanoparticles may be a promising choice as a drug delivery system.

Localized Myocardial Anti-Inflammatory Effects of Temperature-Sensitive Budesonide Nanoparticles during Radiofrequency Catheter Ablation.

Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.

Inhaled Budesonide in Neonatal Respiratory Distress Syndrome of Near-Term Neonates: A Randomized, Placebo-Controlled Trial.

This study evaluates the value of inhaled budesonide (BUD) administration in neonatal respiratory distress syndrome (RDS) cases especially for near-term neonates. A randomized controlled trial involving 120 neonates with respiratory distress, which was diagnosed as RDS, was conducted from July 2016 to March 2018. The neonates studied were divided into 2 groups: group 1 (the inhaled BUD group), consisting of 60 neonates who received BUD (2 mL, 0.25-mg/mL suspension) inhalation, twice daily for 5 days; and group 2 (the placebo group), consisting of 60 neonates with RDS who received humidified distilled sterile water inhalation (2 mL). Downes score, RDS grades, and interleukin 8 (IL-8) levels were monitored and measured on the first and fifth days of incubation. Statistically significant differences (SSDs) in RDS grades, Downes score, and IL-8 levels on the fifth day of admission were observed between groups 1 and 2 (p = 0.001) and between the first and fifth days of incubation in group 1 (p = 0.001). The SSDs in the duration of hospitalization (p = 0.001) and the number of neonates receiving mechanical ventilation (p = 0.032) were found between both groups. Budesonide inhalation is associated with improvements in clinical and laboratory parameters in neonates with RDS.

The efficacy and safety of azithromycin in treatment for childhood asthma: A systematic review and meta-analysis.

Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma. We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratioswith 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled. We included 19 eligible reports from 17 studies. The prevalence of exacerbations in AZI + budesonide (BUD) + β2 agonist (BA) group was lower than BUD + BA group (four [13%] vs. 19 [63%], p < 0.05) in 6- 14 years old children with chronic persistent asthma. AZI plus antiasthma drugs (AADs) could improve the posttreatment childhood asthma control test score (MD = 2.97; 95% CI, 2.39-3.54) compared to AADs alone in children with chronic persistent asthma. AZI plus AADs could improve posttreatmentforced expiratory volume in 1 s of predicted value/forced vital capacity % (MD = 10.24%; 95% CI, 6.44%-14.03%) and posttreatment peak expiratory flow % of predicted value (MD = 7.00%; 95% CI, 2.53%-11.47%) compared to AADs alone in children with chronic persistent asthma. The most common adverse reactions of AZI combined with other drugs were gastrointestinal reactions. AZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

β-Cyclodextrin Inclusion Complexes of Budesonide with Enhanced Bioavailability for COPD Treatment

Chronic obstructive pulmonary disease (COPD) is a life-threatening disease of the respiratory system, affecting many patients worldwide. Budesonide (BUD), a synthetic glucocorticosteroid applied for the treatment of COPD patients, is a hydrophobic compound with low bioavailability. The formation of inclusion complexes of hydrophobic compounds with β-cyclodextrin (CD) through the solvent evaporation technique is an appealing method for the amelioration of the compounds’ in vitro release behavior. In the present study, CD–BUD complexes were prepared through the solvent evaporation technique. The effect of the applied solvent was evaluated through FTIR, scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and in vitro release behavior measurements. It was found that the optimum complexes with the minimum degree of crystallinity and the optimum in vitro release behavior are prepared in the solvent ratio H2O/EtOH 80/20 v/v. In a further step, the formation of CD–BUD complexes containing different amounts of BUD was prepared. Through XRD measurements, the degree of crystallinity of the samples was calculated confirming the diminished crystallinity of BUD in CD complexes. The in vitro release of the samples showed the improved release behavior of BUD from the complexes in comparison to neat BUD while a direct correlation between the degree of crystallinity and in vitro release behavior was demonstrated.