Search Results (27)

Background: Inhaled corticosteroids (ICSs) are a cornerstone in asthma management, particularly during exacerbations, when high doses are often prescribed. However, patient concerns about potential side effects such as increased appetite, weight gain, and metabolic disturbances may reduce adherence, compromising treatment outcomes. While oral corticosteroids (OCSs) are well known to induce such effects, the metabolic impact of short-term high-dose ICSs remains poorly studied. Objective: This prospective pilot study aimed to assess whether a 14-day course of high-dose ICSs in adults with stable asthma induces changes in appetite, dietary intake, leptin levels, or body weight. Methods: Thirty-five adults (19 males, 16 females; mean age 48.7 ± 15.1 years) with stable mild asthma received ≥400 µg/day extrafine beclomethasone dipropionate/formoterol via pressurized metered-dose inhaler for 14 days. Participants underwent assessments at baseline and after 14 days, including body weight, BMI, fasting serum leptin levels, dietary intake (evaluated using 24 h dietary recalls), and appetite (measured via a visual analogue scale). Results: No significant changes were observed in body weight (mean change: −0.38 kg; 95% CI: −0.81 to 0.05; p = 0.083) or BMI (p = 0.912) following high-dose ICS use. Similarly, serum leptin levels (mean change: 0.13 ng/mL; 95% CI: −3.47 to 3.72; p = 0.945), subjective appetite scores (mean change: −4.93 mm; 95% CI: −13.64 to 3.79; p = 0.267), and dietary energy intake (mean change: +255 kJ/day; 95% CI: −380 to 891; p = 0.431) did not differ significantly post-intervention. Conclusions: Short-term high-dose ICS therapy in adults with mild asthma may not significantly affect appetite, dietary intake, leptin levels, or body weight. These findings support the metabolic safety of short-term high-dose ICSs and may help alleviate patient concerns, improving adherence during exacerbation management. Full article

Background: Nasal steroids are commonly prescribed in ear, nose, and throat clinics. It is observed that the use of nasal steroids is increasing due to the prevalence of allergic rhinitis. Because beclomethasone (BCM) toxicity is low, it is highly preferred in allergic rhinitis. The rate of toxicity increases with the increase in the duration and dose of BCM use. However, the protective mechanism of Anatolian propolis (AP) and curcumin (Cur) against BCM toxicity has not been fully explained. Aim: The study evaluates the potential BCM-induced toxicity effect on VEGF, MMP-2, IL-25, and IL-10 parameters after Cur and AP treatment. Materials and Methods: Cell viability, oxidative stress, and gene expression were used for toxicity evaluation. Results: AP 2.5 mg/mL and Cur 16 µg/mL show high viability and antioxidant capacity. BCM increased the levels of IL-25, IL-10, and MMP-2, and a decrease was detected in the expression levels of FGF-2 and VEGF. Conclusions: AP and Cur show effective healing, and AP has been shown to improve inflammation more effectively than Cur. However, the combination of AP and Cur significantly improved the induced toxicity effects. Full article

The analysis of cosmetic products represents an important field of analytical chemistry, since the demand for new formulations is continuously increasing. Regulations about prohibited/regulated compounds are applied in each country. Among the substances that are banned in cosmetics, corticosteroids represent a potential harm for consumers since the prolonged exposure to these compounds can affect health status. However, corticosteroids can be found in cosmetics as an illegal addition since they are able to alleviate the symptoms of inflammatory skin problems. In this work, two different approaches for detecting corticosteroids as potential adulterants in cosmetic products were compared. First, a reversed-phase HPLC-MS method was optimized and fully validated in order to identify and quantify eight corticosteroids (methylprednisolone, beclomethasone, flunisolide, budesonide, betamethasone 17-valerate, beclomethasone dipropionate, flumethasone, and dexamethasone). This reference method was then compared with an enzyme-linked immunosorbent assay (ELISA). Indeed, immunological techniques allow for rapid, low-cost, and sensitive detection of target analytes even in complex matrices, and they can be performed with simple instrumentation and by non-skilled personnel. The application of these methods on spiked cosmetic products was compared in terms of performance and advantages in order to evaluate the possibility of exploiting a complementary approach for optimizing the time for and costs of the analysis. Full article

Background: Genetic factors play a role in asthma severity. However, low- and middle-income countries have minimal contribution to genomic asthma research. The current study investigates the influence of an important genetic asthma region (6p21) on severe asthma in a cohort of asthmatics in Pakistan. Materials and Methods: In this case–control study, mild to severe asthmatic patients (n = 255) and controls (n = 260) were enrolled from Lahore, Pakistan. Blood samples were collected, and genomic DNA was extracted for the genotyping of 11 single nucleotide polymorphisms located in the 6p21 region. Severe asthma was defined based on the defined daily dose of inhaled corticosteroids equivalent to 200 mcg of beclomethasone dipropionate (as per the global initiative for asthma guidelines). An additive genetic model was followed to find the associations between these variants and the outcome. Univariate and multivariate logistic regression, adjusted for confounders, was performed. Odds ratio (OR), 95% confidence interval (95% CI), p-value, and q-values after FDR adjustment were estimated. Results: The genetic variants rs3025028, rs987870, and rs3025039 showed strong associations with the incidence of asthma with odds ratios of 1.58, 1.62, and 2.70 (95% CI = 1.16–2.16, 1.15–2.30, and 1.40–5.39, respectively). Further stratification analysis to study the risk of severe asthma also revealed markedly significant associations for rs3025020 and rs1799964 (OR = 2.28 and 2.99; 95% CI = 1.39–3.86 and 1.75–5.33, respectively). However, the SNPs rs2070600, rs987870, and rs3025039 also showed a significant relationship with the severity (OR = 2.34, 1.75, and 2.72; 95% CI = 1.02–5.97, 1.07–2.98, and 1.11–7.71, respectively), but FDR-adjusted q-values were insignificant (0.10, 0.07, and 0.07, respectively). Conclusions: The 6p21 region variants rs3025028, rs987870, and rs3025039 are associated with the incidence, whereas rs3025020 and rs1799964 are associated with the risk of more severe asthma in the Pakistani population. Full article

Background: Spray drying, whilst a popularly employed technique for powder formulations, has limited applications for large-scale proliposome manufacture. Objectives: Thus, the aim of this study was to investigate spray drying parameters, such as inlet temperature (80, 120, 160, and 200 °C), airflow rate (357, 473, and 601 L/h) and pump feed rate (5, 15, and 25%), for individual carbohydrate carriers (trehalose, lactose monohydrate (LMH), and mannitol) for 24 spray-dried (SD) formulations (F1–F24). Methods: Following optimization, the SD parameters were trialed on proliposome formulations based on the same carriers and named as spray-dried proliposome (SDP) formulations. Drug delivery of the formulations was assessed using a dry powder inhaler (DPI) in combination with a next-generation impactor (NGI). Results: Upon analysis, formulations F6 (SD-mannitol), F15 (SD-trehalose), and F20 (SD-LMH) demonstrated high production yields (84.01 ± 3.25, 72.55 ± 5.42, and 70.03 ± 3.39%, respectively), small particle sizes (2.96 ± 1.42, 4.55 ± 0.46, and 5.16 ± 1.32 µm, respectively) and low moisture contents (0.25 ± 0.03, 3.76 ± 0.75, and 1.99 ± 0.77%). These SD optimized parameters were then employed for SDP formulations employing dimyristoly phosphatidylcholine (DMPC) as a phospholipid and beclomethasone dipropionate (BDP) as the model drug. Upon spray drying, SDP-mannitol provided the highest production yield (82.45%) and smallest particle size (2.64 µm), as well as high entrapment efficiency (98%) and a high fine particle dose, fine particle fraction, and respirable fraction (285.81 µg, 56.84%, 86.44%, respectively). Conclusions: The study results are a promising step in the optimization of the large-scale manufacture of proliposome formulations and highlight the versatility of the instrument and variability of formulation properties with respect to the carriers employed for targeting the pulmonary system using dry powder inhalers. Full article

Background/Objectives: This study focuses on the ability of vaping technology to deliver beclomethasone dipropionate compared to nebulization. Methods: An in vitro comparison of aerosol properties in terms of respirable dose with the Glass Twin Impinger and the mass median aerodynamic diameter using the Next Generation Impactor was performed. The respirable dose delivered in a vaping drug delivery system (VDDS) puff as a function of concentration was quantified by high-pressure liquid chromatography coupled with an ultraviolet detector. Results: The mass of drug contained in a single puff of 55 mL of aerosol varied between 0.94 and 1.95 µg for a refill liquid concentration range of 400 to 1600 µg/mL. The analysis of the particle size distribution shows an advantage for a VDDS in producing smaller particles compared to nebulization (1.56 ± 0.05 µm vs. 2.30 ± 0.19 µm). In total, 81 puffs are needed to reach the dose equivalent to nebulized beclomethasone dipropionate under these specific experimental conditions, which corresponds to an aerosol duration of about 4 min (i.e., four times lower than the jet nebulizer) and a patient administration time of about 45 min (i.e., three times higher than the jet nebulizer). Conclusions: The results show the potential of vaping devices as an alternative to nebulizers for the administration of beclomethasone dipropionate in an equivalent respirable dose. Full article

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”. Full article

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. Full article

In recent years, some new concepts have been added to asthma treatment such as “anti-inflammatory reliever” (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. Full article

The gut microbiota plays an important role in the physiological activities of the host and affects the formation of important economic traits in livestock farming. The effects of cecal microbiota on chicken weights were investigated using the Guizhou yellow chicken as a model. Experimental cohorts from chickens with high- (HC, n = 16) and low-market-weights (LC, n = 16) were collected. Microbial 16S rRNA gene sequencing and non-targeted serum metabolome data were integrated to explore the effect and metabolic mechanism of cecal microbiota on market weight. The genera Lachnoclostridium, Alistipes, Negativibacillus, Sellimonas, and Ruminococcus torques were enriched in the HC group, while Phascolarctobacterium was enriched in the LC group (p < 0.05). Metabolomic analysis determined that pantothenic acid (vitamin B5), luvangetin (2H-1-benzopyran-6-acrylic acid), and menadione (vitamin K3) were significantly higher in HC serum, while beclomethasone dipropionate (a glucocorticoid) and chlorophene (2-benzyl-4-chlorophenol) were present at higher levels in the LC group. The microbes enriched in HC were significantly positively correlated with metabolites, including pantothenic acid and menadione, and negatively correlated with beclomethasone dipropionate and chlorophene. These results indicated that specific cecal bacteria in Guizhou yellow chickens alter the host metabolism and growth performance. This study provides a reference for revealing the mechanism of cecal microbe actions that affect chicken body weight. Full article

Medical composites derived from Gamma-cyclodextrin (γ-CD) and beclomethasone dipropionate−gamma-cyclodextrin (BDP−γ-CD) are synthesized over supercritical-assisted atomization (SAA) herein. Carbon dioxide, which serves the dual function of spraying medium and co-solute, is incorporated in this process along with the ethanolic solvent. Results indicate that, for fine spherical particles, optimized aerosol performance could be obtained with 50.0% (w/w) ethanolic solvent, precipitator, and saturator at 373.2 K and 353.2 K, respectively, and carbon dioxide-to-γ-CD flow ratio of 1.8 in the presence of 10 wt% leucine (LEU) as dispersion enhancer. It is also noted that γ-CD solution at low concentration typically renders better aerosol performance of the particles. During drug particle-derivation, the solubility of drug BDP elevated considerably due to the formation of inclusion complexes, further assisted by the ethanolic solvent which increases the lipophilicity of BDP. Meanwhile, the in vitro aerosolization and dissolution performance of drug composites derived from varied γ-CD-to-BDP mass ratio (Z) were also evaluated. It was found that high Z promises higher fine particle fraction in the obtained drug composite while the dissolution rate of active ingredient (BDP) exhibits positive correlation to the content of water-soluble excipient (γ-CD) in the formulation. This study offers a new avenue for instant drug formulation with promising pulmonary delivery over the SAA technique. Full article

Allergic Rhinitis (AR) is a chronic inflammatory disease of sino-nasal mucosa, is IgE-mediated, and affects 10–40% of the global population. This study aimed to compare the efficacy of nasal administration of Beclomethasone Dipropionate (BDP) delivered via Spray-sol with nasal spray in patients suffering from AR. We included 28 AR patients assigned to one of the two following treatments: the Spray-sol group (BDP via Spray-sol) (n = 13) and the spray group (BDP using a common nasal spray) (n = 15). Both treatments were administered twice daily for 4 weeks. A nasal endoscopy evaluation and Total Nasal Symptom Score were performed at baseline and after treatment. The Spray-sol group showed better results than the spray group regarding nasal endoscopy (edema, p < 0.01; irritation, p < 0.01; secretion, p < 0.01) and nasal symptoms (nasal congestion, p < 0.05; rhinorrhea, p < 0.05; sneezing, p < 0.05; and total score, p < 0.05). No side effects were recorded. These data supported the fact that the use of BDP delivered with Spray-sol is more effective than BDP nasal spray in AR patients. Further studies are needed to confirm these encouraging results. Full article

Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl–cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (d_aer) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMAD_exp). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil^®. In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8. Full article

Lipid-based nanoparticles (LBNs) are a new type of nanoparticulate drug-delivery system, which have gradually demonstrated broad prospects in pulmonary drug-delivery systems. However, the main disadvantage of these LBNs for inhalable drugs with limited lipophilicity is their low encapsulation capacity. Herein, this study anticipates establishing a technology platform to improve the loading capacity of low-lipophilicity drugs in LBNs for the therapy of lung diseases. A proof-of-concept study was carried out using Beclomethasone dipropionate (BDP) as a model drug. BDP was conjugated with stearic acid (SA), a kind of the lipid matrix for LBN. The conjugate was characterized and the interactions between the conjugate and SA were investigated via molecular dynamics simulation. It is expected that the drug-loading capacity of weak-lipophilic drugs in LBN can be increased by establishing the technology platform, and the application of LBNs in pulmonary delivery can be broadened. Full article

Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student’s t-test or Welch’s t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)₂D₃ had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs. Full article