Purpose: There is a need to generate new treatments against pulmonary diseases such as idiopathic fibrosis and asthma. N-acetylcysteine (NAC) has multiple clinical applications, but its unstable nature and route of administration limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC's limitations. This work aims to evaluate the efficacy of NAC combined with liposomes as a treatment for asthma and in preventing fibrotic development.

Methods: Unilamellar vesicles were obtained through the dehydration-rehydration method followed by multiple membrane extrusion and characterized by Dynamic Light Scattering and Transmission electron microscopy. Lung fibrosis was induced by bleomycin administration, and liposomal formulation of NAC (LipoNAC) was evaluated as a preventive treatment. LipoNAC formulation was also evaluated in a therapeutic regimen for asthma using the classic ovalbumin model. For both models, the administration of the treatment was via the intranasal route.

Results: NAC treatments (free NAC and LipoNAC) improved lung histopathology and decreased collagen deposition when tested in the lung fibrosis model. Only LipoNAC decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-β. Although both treatments decreased Th2 cytokine and histopathological inflammation in the asthma model, only LipoNAC treatment significantly decreased mucus in asthmatic mice.

Conclusions: These results indicate that surfactant liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, rendering it a promising therapy for respiratory diseases.

Keywords: Asthma; Idiopathic pulmonary fibrosis; Liposomes; Lung surfactants; N-acetylcysteine; Respiratory diseases.

Copyright © 2025. Published by Elsevier Inc.

目的： 有必要针对特发性肺纤维化和哮喘等肺部疾病开发新的治疗方法。N-乙酰半胱氨酸（NAC）具有多种临床应用，但由于其不稳定性以及给药途径的限制，影响了其疗效。新的肺部递送策略，如使用肺表面活性剂脂质制成的脂osome，可以克服NAC的这些局限性。本研究旨在评估结合使用NAC和脂osome治疗哮喘及预防纤维化发展的效果。

方法： 单层囊泡通过脱水-复水法并经过多次膜挤压后获得，并通过动态光散射（Dynamic Light Scattering）和透射电子显微镜进行表征。肺纤维化是通过给药博来霉素诱导的，NAC脂osome制剂（LipoNAC）被评估为预防性治疗方案。在哮喘的经典卵清蛋白模型中也对LipoNAC疗法进行了评估。对于两个模型中的治疗均采用鼻内递送途径。

结果： NAC治疗（自由形式的NAC和LipoNAC）在肺纤维化模型测试中改善了肺部组织病理学并减少了胶原沉积。仅LipoNAC降低了血清乳酸脱氢酶水平、肺液中的髓过氧化物酶活性以及肺TGF-β水平。虽然两种治疗方案均减轻了哮喘模型中的Th2细胞因子和炎症，但只有LipoNAC治疗显著减少了哮喘小鼠的粘液分泌。

结论： 这些结果显示，使用表面活性剂脂osome递送NAC可以增强其抗炎、溶解黏液以及抗氧化的作用，使其成为呼吸系统疾病的有前景的治疗方法。

关键词： 哮喘；特发性肺纤维化；脂osome；肺表面活性剂；N-乙酰半胱氨酸；呼吸系统疾病。