This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

中文翻译：

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通过模拟病毒纳米颗粒增强呼吸系统疾病的肺部输送和免疫调节


本研究介绍了专为有效肺部药物输送而设计的纳米溴己新脂质颗粒（NBL）平台。受呼吸道病毒转运机制的启发，NBL 解决了肺部疾病中与粘液渗透和炎症相关的挑战。 NBL 由低分子量聚乙二醇包被的脂质纳米颗粒和盐酸溴己新组成，尺寸为 118 ± 24 nm，中性 zeta 电位，渗透压为 358 ± 28 mOsmol/kg，pH 为 6.5。 NBL 雾化无渗漏，对上皮细胞无毒性，具有粘膜粘附特性​​，粘蛋白结合效率为 60%。它们有效地穿过空气-液体界面中 Calu-3 培养物的致密粘液层，与未暴露的细胞相比，MUC5AC 密度降低了 55%，纳米颗粒内化增加了 29%。在评估免疫调节作用时，NBL 治疗 SARS-CoV-2 感染的肺细胞导致抗炎 MUC1 基因表达增加 40 倍，促炎性 IL-6 表达成比例减少，抗炎性 IL 升高-10 表达式。这些发现表明了调节病毒感染引发的 IL-6 过度表达的潜在机制。因此，NBL 平台展示了高效肺部药物输送和免疫调节的巨大潜力，为解决肺部疾病中的粘液渗透和炎症提供了一种新方法。