Search results for: Budesonide

Authors: Rakan Hassan M. Alzahrani, Ziyad Alzahrani, Bader Bashrahil, Abdulrahman Elyasi, Abdullah a Ghaddaf, Rayan Alzahrani, Mohammed Alkathlan, Nawaf Alghamdi, Dakheelallah Almutairi

Abstract:

Background: Corticosteroid irrigations, which regularly involve the off-label use of budesonide mixed with normal saline in high volume Sino-nasal irrigations, have been more commonly used in the management of post-operative chronic rhinosinusitis (CRS). Objective: This article attempted to measure the efficacy of post-operative budesonide nasal irrigation compared to normal saline-alone nasal irrigation in the management of chronic rhinosinusitis (CRS) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: The databases PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched by two independent authors. Only RCTs comparing budesonide irrigation to normal saline alone irrigation for CRS with or without polyposis after functional endoscopic sinus surgery (FESS) were eligible. A random effect analysis model of the reported CRS-related quality of life (QOL) measures and the objective endoscopic assessment scales of the disease was done. Results: Only 6 RCTs met the eligibility criteria, with a total number of participants of 356. Compared to normal saline irrigation, budesonide nasal irrigation showed statically significant improvements in both the CRS-related quality of life (QOL) and the endoscopic findings (MD= -4.22 confidence interval [CI]: -5.63, -2.82 [P < 0.00001]), (SMD= -0.50 confidence interval [CI]: -0.93, -0.06 [P < 0.03]) respectively. Conclusion: Both intervention arms showed improvements in CRS-related QOL and endoscopic findings in post-FESS chronic rhinosinusitis with or without polyposis. However, budesonide irrigation seems to have a slight edge over conventional normal saline irrigation with no reported serious side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression.

Keywords: Budesonide, chronic rhinosinusitis, corticosteroids, nasal irrigation, normal saline

Procedia PDF Downloads 79

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

Abstract:

In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 248

Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

Abstract:

Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

Procedia PDF Downloads 522