Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Cairo, Egypt.
Drug Deliv. 2021 Dec;28(1):826-843. doi: 10.1080/10717544.2021.1905747.
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 (< .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.
环索奈德（CIC）是一种吸入性皮质类固醇药物，用于治疗支气管哮喘，目前以计量吸入器（CIC-MDI）的形式提供，这在老年人、危重症患者和儿童的管理中存在重大挑战。在这项工作中，制备了雾化环索奈德纳米结构脂质颗粒（CIC-NLPs），并对其进行了深入的肺部给药和细胞毒性评估，以便以可控的方式和较低的剂量为患者提供额外的临床益处。还评估了与商业（CIC-MDI）相比，在卵清蛋白（OVA）诱导的哮喘 Balb/c 小鼠中雾化后产生的生物功效。成功包封了 222.6nm 的 CIC 的开发型 NLPs（包封效率 93.3%），并在较低的撞击器阶段表现出良好的雾化效率（质量中值空气动力学直径（MMAD）为 2.03μm，细颗粒分数（FPF）为 84.51%），表明没有任何细胞毒性作用，可达到 100μg/ml 的浓度。与商业 CIC-MDI 吸入器（Alvesco）的 80μg 剂量相比，雾化 40μg 剂量的开发型 CIC-NLPs 可显著减轻过敏气道炎症，这表明具有显著的治疗作用。通过显著降低（<0.0001）促炎细胞因子 IL-4 和 13、血清 IgE 水平、丙二醛（MDA）、一氧化氮（NO）、TNF-α 和活性核因子-κB（NF-κB）活性，以及同时增加超氧化物歧化酶（SOD）活性，可观察到优异的抗炎和抗氧化应激作用。与观察到的生化改善相关的是，呼吸道炎症细胞浸润的组织学检查得到了很好的抑制。
