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<p>Nintedanib esylate (NE), a bifunctional tyrosine kinase inhibitor, is clinically approved for managing idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC). However, its clinical use is limited by poor aqueous solubility and low oral bioavailability. This study aimed to develop a controlled-release dry powder inhaler (DPI) based on lyophilized albumin nanocomposites (ALBNCs) to enhance pulmonary drug delivery and improve biopharmaceutical performance. NE-loaded ALB nanoparticles (ALBNPs) were prepared using the desolvation method and subsequently lyophilized. The NE-ALBNCs-based dry powder formulation exhibited a particle size of 2.318 ± 0.56&#xa0;μm, a zeta potential of -35.8 mV, and a drug content of 88 ± 0.12%, indicating its favorable physicochemical characteristics. The in vitro release study demonstrated that 83.47 ± 1.28% of NE was released over 50&#xa0;h, indicating a sustained drug release profile. The ALBNCs demonstrated favorable aerodynamic performance, with a mass median aerodynamic diameter (MMAD) of 1.75 ± 0.19&#xa0;μm and a fine particle fraction (FPF) of 60.33 ± 0.38%, as determined using an Anderson cascade impactor. The cytotoxicity study and antifibrotic activity against A549 and LL29 cell lines were assessed and depicted significant inhibition of tumor cell growth and antifibrotic activity. ALBNCs exhibited 4 times higher area under the curve (AUC) as compared to the conventional form of DPI. Histopathological evaluation demonstrated no evidence of severe pulmonary toxicity. The developed bifunctional ALBNCs may offer a promising strategy for targeted therapy in IPF and NSCLC, representing a potential advancement in translational research aimed at bridging preclinical development and clinical application.</p> Graphical abstract <p></p>

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Inhalable Biopolymer-based Nanocomposites of Nintedanib Esylate: Design, Pharmacokinetics, Cytotoxicity and Antifibrotic Assessment

  • 期刊论文

  • 发表日期：

    2026年7月2日

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  • Sakshi Kumbhar,
  • Prajwal Lonkar,
  • Ravindra Kulkarni,
  • Prakash Jadhav,
  • Chellampillai Bothiraja,
  • Rajavi Karaveershettar,
  • Atmaram Pawar,
  • Ashwin Mali

摘要

Nintedanib esylate (NE), a bifunctional tyrosine kinase inhibitor, is clinically approved for managing idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC). However, its clinical use is limited by poor aqueous solubility and low oral bioavailability. This study aimed to develop a controlled-release dry powder inhaler (DPI) based on lyophilized albumin nanocomposites (ALBNCs) to enhance pulmonary drug delivery and improve biopharmaceutical performance. NE-loaded ALB nanoparticles (ALBNPs) were prepared using the desolvation method and subsequently lyophilized. The NE-ALBNCs-based dry powder formulation exhibited a particle size of 2.318 ± 0.56 μm, a zeta potential of -35.8 mV, and a drug content of 88 ± 0.12%, indicating its favorable physicochemical characteristics. The in vitro release study demonstrated that 83.47 ± 1.28% of NE was released over 50 h, indicating a sustained drug release profile. The ALBNCs demonstrated favorable aerodynamic performance, with a mass median aerodynamic diameter (MMAD) of 1.75 ± 0.19 μm and a fine particle fraction (FPF) of 60.33 ± 0.38%, as determined using an Anderson cascade impactor. The cytotoxicity study and antifibrotic activity against A549 and LL29 cell lines were assessed and depicted significant inhibition of tumor cell growth and antifibrotic activity. ALBNCs exhibited 4 times higher area under the curve (AUC) as compared to the conventional form of DPI. Histopathological evaluation demonstrated no evidence of severe pulmonary toxicity. The developed bifunctional ALBNCs may offer a promising strategy for targeted therapy in IPF and NSCLC, representing a potential advancement in translational research aimed at bridging preclinical development and clinical application.

Graphical abstract