BACKGROUND Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. RESULTS The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. CONCLUSIONS Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

中文翻译：

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通过中性粒细胞抑制作用减轻小鼠急性呼吸窘迫综合征的基于油酸的纳米系统：颗粒大小如何影响治疗效率。

背景技术据报道，油酸（OA）对活化的中性粒细胞显示出抗炎活性。它也是纳米颗粒中增加稳定性和细胞内在化的重要材料。我们旨在评估可注射的基于OA的纳米颗粒治疗肺损伤的抗炎活性。制备了不同尺寸的纳米载体以探索纳米颗粒尺寸对炎症抑制的影响。结果纳米粒子的平均直径为105、153和225 nm。纳米载体在5分钟的时间内被分离的人类嗜中性粒细胞摄取，较小的颗粒表现出更大的摄取。尺寸减小导致细胞活力和细胞内钙水平降低。负载OA的纳米系统剂量依赖性地抑制了受刺激的中性粒细胞产生的超氧阴离子和弹性蛋白酶。对于不同尺寸的纳米颗粒，抑制水平是可比的。在离体生物分布研究中，纳米粒子的肺累积随着粒径的增加而增加。纳米载体主要通过肝脏和胆汁清除而排泄。将小鼠暴露于气管内脂多糖（LPS）以诱导急性呼吸窘迫综合征（ARDS），例如肺损伤。与OA溶液相比，基于脂质的纳米载体可更有效地缓解髓过氧化物酶（MPO）和细胞因子。与较小的纳米颗粒相比，较大的纳米颗粒对MPO，TNF-α和IL-6的还原作用更大。组织学证实，静脉内施用较大的纳米颗粒后，肺中性粒细胞募集和肺结构损伤减少。结论纳米颗粒大小是支配抗炎作用和肺损伤治疗的基本特性，对活化的中性粒细胞抑制作用和体内治疗功效具有不同的作用。