1. Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks.
- Author
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El-Laithy HM, Youssef A, El-Husseney SS, El Sayed NS, and Maher A
- Subjects
- Administration, Inhalation, Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents pharmacology, Cell Line, Cell Survival, Dose-Response Relationship, Drug, Drug Liberation, Female, Humans, Inflammation Mediators metabolism, Mice, Mice, Inbred BALB C, Nanoparticles, Particle Size, Pregnenediones administration & dosage, Pregnenediones pharmacology, Surface Properties, Anti-Inflammatory Agents pharmacokinetics, Lung metabolism, Nebulizers and Vaporizers, Pregnenediones pharmacokinetics
- Abstract
Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available as metered dose inhaler (CIC-MDI) which possesses a major challenge in the management of the elderly, critically ill patients and children. In this work, nebulized CIC nano-structure lipid particles (CIC-NLPs) were prepared and evaluated for their deep pulmonary delivery and cytotoxicity to provide additional clinical benefits to patients in controlled manner and lower dose. The bio-efficacy following nebulization in ovalbumin (OVA) induced asthma Balb/c mice compared to commercial (CIC-MDI) was also assessed. The developed NLPs of 222.6 nm successfully entrapped CIC (entrapment efficiency 93.3%) and exhibited favorable aerosolization efficiency (mass median aerodynamic diameter (MMAD) 2.03 μm and fine particle fraction (FPF) of 84.51%) at lower impactor stages indicating deep lung deposition without imparting any cytotoxic effect up to a concentration of 100 μg/ml. The nebulization of 40 µg dose of the developed CIC-NLPs revealed significant therapeutic impact in the mitigation of the allergic airways inflammations when compared to 80 µg dose of the commercial CIC-MDI inhaler (Alvesco
® ). Superior anti-inflammatory and antioxidative stress effects characterized by significant decrease ( p < .0001) in inflammatory cytokines IL-4 and 13, serum IgE levels, malondialdehyde (MDA), nitric oxide (NO), TNF-α, and activated nuclear factor-κB (NF-κB) activity were obvious with concomitant increase in superoxide dismutase (SOD) activity. Histological examination with inhibition of inflammatory cell infiltration in the respiratory tract was correlated well with observed biochemical improvement.- Published
- 2021
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