Nebulized inhalation of nintedanib-loaded biomimetic nano-liposomes attenuated bleomycin-induced interstitial lung fibrosis in mice

• DOI: 10.1016/j.nantod.2024.102298
• Publication Date: 2024-05-08T19:45:23Z
• Authors: Le Rao; Pingjun Zhu; Mengyu Guo; Mingdi Hu; Xiaocui Guo; Yingzhen Du; Guogang Xu
• Keywords: Nintedanib; Lung Fibrosis

Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial lung disease with a poor prognosis. However, there are currently few drugs available for its treatment. Nintedanib clinically effective but associated gastrointestinal adverse effects and weight loss. Due to drug intolerance, the overall outcomes of nintedanib therapy substantially compromised in quite patients. In present study, we synthesized nintedanib-loaded biomimetic liposomes (Nin-lipo) improve antifibrotic efficacy tolerance nintedanib. It was observed that nebulized inhalation small doses Nin-lipo (2 mg/kg) resulted greater delivery efficiency higher concentrations tissue than conventional oral (60 mg/kg). Furthermore, significantly inhibited bleomycin (BLM)-induced improved function mice. The possible molecular mechanism anti-fibrosis by investigated. found act mechanistically on alveolar macrophages via surfactant proteins A D (SP-A/D) simulating surfactants inhibiting polarization M2 macrophages. These thereby reduced secretion transforming growth factor 1 (TGF-β1) Moreover, demonstrated significant against loss liver abnormalities mouse model caused Therefore, could greatly while maintaining excellent safety profile. potentially be developed as new IPF.