Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks.

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.

• Authors: Hanan M El-Laithy, Amal Youssef, Shereen S El-Husseney, Nesrine S El Sayed, Ahmed Maher
• Journal: Drug delivery (Drug Deliv) Vol. 28 Issue 1 Pg. 826-843 (Dec 2021) ISSN: 1521-0464 [Electronic] England
• PMID: 33928836 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Inflammation Mediators
• Pregnenediones
• ciclesonide

Topics

• Administration, Inhalation
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacokinetics, pharmacology)
• Cell Line
• Cell Survival
• Dose-Response Relationship, Drug
• Drug Liberation
• Female
• Humans
• Inflammation Mediators (metabolism)
• Lung (metabolism)
• Mice
• Mice, Inbred BALB C
• Nanoparticles
• Nebulizers and Vaporizers
• Particle Size
• Pregnenediones (administration & dosage, pharmacokinetics, pharmacology)
• Surface Properties