Pan Bo, Wu Fangping, Lu Shanming, Lu Wenwen, Cao Jiahui, Cheng Fei, Ou Meitong, Chen Youyi, Zhang Fan, Wu Guolin, Mei Lin
The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
Department of Pathology, Longgang Central Hospital, Shenzhen, Guangdong, 518100, China.
Small Methods. 2025 Jul;9(7):e2400980. doi: 10.1002/smtd.202400980. Epub 2024 Oct 6.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by sustained fibrotic lesions. Orally administered drugs usually fail to efficiently penetrate the interstitial tissue and reach the lesions, resulting in low treatment efficiency. Luteolin (Lut) is a natural flavonoid, active metabolites of which possess antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. In this study, a nano-formulation is developed by loading Lut into hyaluronidase nanoparticles (Lut@HAase). These Lut@HAase nanoparticles (NPs) exhibit small size and good stability, suitable for noninvasive inhalation and accumulation in the lungs, and hyaluronidase at the site of lesions can degrade hyaluronic acid in the interstitial tissue, enabling efficient penetration of Lut. Lut's therapeutic effect, when administered via NPs, is studied both in vitro (using MRC5 cells) and in vivo (using IPF mice models), and its anti-fibrotic properties are found to inhibit inflammation and eliminate reactive oxygen species. Conclusively, this study demonstrates that Lut@HAase can improve lung function and enhance survival rates while reducing lung damage with few abnormalities during IPF treatment.
特发性肺纤维化（IPF）是一种以持续性纤维化病变为特征的慢性进行性间质性肺疾病。口服药物通常无法有效穿透间质组织并到达病变部位，导致治疗效率低下。木犀草素（Lut）是一种天然黄酮类化合物，其活性代谢产物具有抗氧化、抗炎、抗纤维化和抗凋亡特性。在本研究中，通过将Lut负载到透明质酸酶纳米颗粒（Lut@HAase）中制备了一种纳米制剂。这些Lut@HAase纳米颗粒（NPs）尺寸小且稳定性好，适合无创吸入并在肺部蓄积，病变部位的透明质酸酶可降解间质组织中的透明质酸，使Lut能够有效渗透。通过纳米颗粒给药时，Lut的治疗效果在体外（使用MRC5细胞）和体内（使用IPF小鼠模型）均进行了研究，发现其抗纤维化特性可抑制炎症并清除活性氧。总之，本研究表明，Lut@HAase在IPF治疗期间可改善肺功能、提高生存率，同时减少肺损伤且几乎无异常。
