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<p>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease marked by relentless deterioration of pulmonary function. Clinically, oral pharmacotherapy for IPF is hampered by two major limitations: inefficient drug delivery to the lung parenchyma and systemic exposure leading to unavoidable off-target side effects. In this study, we developed an inhalable tanshinone IIA (TA) formulation based on lipid nanocrystals to address these challenges. Leveraging the high drug loading capacity and structural stability of lipid nanocrystals, this platform overcomes the intrinsic hydrophobicity of TA, thereby markedly improving its aqueous dispersibility, aerosolization performance, and regional deposition in the deep lung. In vitro, TA lipid nanocrystals significantly enhanced cellular uptake in both pulmonary epithelial cells and lung fibroblasts. In vivo, they achieved substantially high and sustained pulmonary drug exposure. In a bleomycin-induced mouse model of IPF, inhaled TA lipid nanocrystals attenuated histopathological fibrosis, preserved lung function, and suppressed chronic inflammation via modulating the PI3K-Akt signaling pathway and the coagulation-fibrinolysis system. Collectively, this study establishes TA as a promising inhaled therapeutic agent for IPF and introduces lipid nanocrystals as a versatile, scalable, and clinically translatable platform for targeted pulmonary delivery in fibrotic and other chronic respiratory diseases.</p> Graphical Abstract <p></p>

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A novel inhalable tanshinone IIA lipid nanocrystal formulation for the enhanced treatment of idiopathic pulmonary fibrosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月24日

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  • Qin Wang,
  • Yun Zhao,
  • Yuanhu Mao,
  • Xiaobo Zhang,
  • Lei Huang,
  • Lei Tang,
  • Yi Chen,
  • Zipeng Gong,
  • Jianqing Peng

摘要

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease marked by relentless deterioration of pulmonary function. Clinically, oral pharmacotherapy for IPF is hampered by two major limitations: inefficient drug delivery to the lung parenchyma and systemic exposure leading to unavoidable off-target side effects. In this study, we developed an inhalable tanshinone IIA (TA) formulation based on lipid nanocrystals to address these challenges. Leveraging the high drug loading capacity and structural stability of lipid nanocrystals, this platform overcomes the intrinsic hydrophobicity of TA, thereby markedly improving its aqueous dispersibility, aerosolization performance, and regional deposition in the deep lung. In vitro, TA lipid nanocrystals significantly enhanced cellular uptake in both pulmonary epithelial cells and lung fibroblasts. In vivo, they achieved substantially high and sustained pulmonary drug exposure. In a bleomycin-induced mouse model of IPF, inhaled TA lipid nanocrystals attenuated histopathological fibrosis, preserved lung function, and suppressed chronic inflammation via modulating the PI3K-Akt signaling pathway and the coagulation-fibrinolysis system. Collectively, this study establishes TA as a promising inhaled therapeutic agent for IPF and introduces lipid nanocrystals as a versatile, scalable, and clinically translatable platform for targeted pulmonary delivery in fibrotic and other chronic respiratory diseases.

Graphical Abstract