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Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks.
- Source :
-
Drug delivery [Drug Deliv] 2021 Dec; Vol. 28 (1), pp. 826-843. - Publication Year :
- 2021
-
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 <superscript>®</superscript> ). 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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0464
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 33928836
- Full Text :
- https://doi.org/10.1080/10717544.2021.1905747