雾化环索奈德增强肺泡沉积减轻气道炎症:克服计量吸入器缺点的策略
2021/05/26
摘要
环索奈德(CIC)是一种用于支气管哮喘的吸入式皮质类固醇药物，目前通过计量吸入器(CIC- MDI)可用于老年、危重症患者和儿童的治疗，这是一项重大挑战。在本项研究中，我们制备了雾化环索奈德纳米结构脂质颗粒(CIC- nlps)，并对其肺深部输送和细胞毒性进行了评估，以控制方式和更低剂量为患者提供额外的临床益处。对卵清蛋白(OVA)诱导的Balb/c小鼠雾化吸入后的生物功效与CIC-MDI进行了比较。在较低的撞击阶段，所开发的222.6 nm的NLPs成功捕获了CIC(捕获效率93.3%)，并表现出良好的雾化效率(质量中值空气动力学直径(MMAD) 2.03 μm和细颗粒分数(FPF) 84.51%)，表明肺部沉降浓度达到100μg / ml时没有产生任何细胞毒性作用。与80µg商用CIC-MDI吸入器(Alvesco®)相比，40µg雾化吸入已开发的CIC-NLPs在缓解过敏性气道炎症方面具有显著疗效。优越的抗炎和抗氧化应激效应，特点是显著降低(p< .0001)的细胞因子IL-4和IL-13、血清IgE水平、丙二醛(MDA)、一氧化氮(NO)、TNF-α和活化核因子-κB (NF-κB)活性明显升高，同时超氧化物歧化酶(SOD)活性升高。抑制呼吸道炎症细胞浸润的组织学检查与观察到的生化改善密切相关。
Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks
Hanan M El-Laithy , Amal Youssef, Shereen S El-Husseney, Nesrine S El Sayed, Ahmed Maher
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.
环索奈德(CIC)是一种用于支气管哮喘的吸入式皮质类固醇药物，目前通过计量吸入器(CIC- MDI)可用于老年、危重症患者和儿童的治疗，这是一项重大挑战。在本项研究中，我们制备了雾化环索奈德纳米结构脂质颗粒(CIC- nlps)，并对其肺深部输送和细胞毒性进行了评估，以控制方式和更低剂量为患者提供额外的临床益处。对卵清蛋白(OVA)诱导的Balb/c小鼠雾化吸入后的生物功效与CIC-MDI进行了比较。在较低的撞击阶段，所开发的222.6 nm的NLPs成功捕获了CIC(捕获效率93.3%)，并表现出良好的雾化效率(质量中值空气动力学直径(MMAD) 2.03 μm和细颗粒分数(FPF) 84.51%)，表明肺部沉降浓度达到100μg / ml时没有产生任何细胞毒性作用。与80µg商用CIC-MDI吸入器(Alvesco®)相比，40µg雾化吸入已开发的CIC-NLPs在缓解过敏性气道炎症方面具有显著疗效。优越的抗炎和抗氧化应激效应，特点是显著降低(p< .0001)的细胞因子IL-4和IL-13、血清IgE水平、丙二醛(MDA)、一氧化氮(NO)、TNF-α和活化核因子-κB (NF-κB)活性明显升高，同时超氧化物歧化酶(SOD)活性升高。抑制呼吸道炎症细胞浸润的组织学检查与观察到的生化改善密切相关。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Drug Deliv . 2021 Dec;28(1):826-843. doi: 10.1080/10717544.2021.1905747)
(Drug Deliv . 2021 Dec;28(1):826-843. doi: 10.1080/10717544.2021.1905747)
Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks
Hanan M El-Laithy , Amal Youssef, Shereen S El-Husseney, Nesrine S El Sayed, Ahmed Maher
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.
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