Preparation and evaluation of sustained release pirfenidone-loaded microsphere dry powder inhalation for treatment of idiopathic pulmonary fibrosis

Bao, Shixue; Zou, Yi; Firempong, Caleb Kesse; Feng, Yingshu; Yu, Yang; Wang, Ying; Dai, Huiying; Mo, Weiwei; Sun, Changshan; Liu, Hongfei

doi:10.1016/j.ejps.2023.106509

European Journal of Pharmaceutical Sciences

2023

DOI: 10.1016/j.ejps.2023.106509

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Preparation and evaluation of sustained release pirfenidone-loaded microsphere dry powder inhalation for treatment of idiopathic pulmonary fibrosis

Shixue Bao,

Yi Zou,

Caleb Kesse Firempong

et al.

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Cited by 2 publications

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Engineering Macrophage‐Derived Exosome to Deliver Pirfenidone: A Novel Approach to Combat Silicotic Pulmonary Fibrosis

Chen,

Yun,

Tian

et al. 2024

Adv Healthcare Materials

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Silicosis is a severe lung disease characterized by diffuse pulmonary fibrosis, for which there is currently no effective treatment. Pirfenidone (PFD) shows great antifibrotic potential but is clinically hindered by low bioavailability and gastrointestinal side effects. To address these limitations, this study develops a PFD delivery system (PFD‐Exo) using J774A.1 macrophage‐derived exosomes. Firstly, PFD is loaded via sonication, then PFD‐Exo is characterized using Raman spectral imaging and UV absorption spectroscopy. Finally, in vitro and in vivo silicosis models are established to evaluate its antifibrotic effects. Results show that PFD‐Exo outperforms free PFD in inhibiting TGF‐β1‐induced transdifferentiation of primary lung fibroblasts in vitro. In a mouse model of silicosis, PFD‐Exo is found to be accumulated in the lungs following intratracheal administration and significantly ameliorates pulmonary inflammation and fibrosis while minimizing gastrointestinal side effects. Mechanistic studies reveal that PFD‐Exo modulates the TGF‐β signaling pathway by downregulating SMAD3 and upregulating SMAD7 and NOGGIN. In conclusion, this study provides the first evidence of macrophage‐derived exosomes as an effective PFD delivery system for silicosis treatment and offers a promising strategy for other refractory pulmonary diseases.

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Engineering Macrophage‐Derived Exosome to Deliver Pirfenidone: A Novel Approach to Combat Silicotic Pulmonary Fibrosis

Chen,

Yun,

Tian

et al. 2024

Adv Healthcare Materials

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Pirfenidone microcrystals for pulmonary delivery: Regulation of the precipitation behavior in the supercooled droplet

Lu,

Yan,

et al. 2025

International Journal of Pharmaceutics

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Preparation and evaluation of sustained release pirfenidone-loaded microsphere dry powder inhalation for treatment of idiopathic pulmonary fibrosis

Cited by 2 publications

References 76 publications

Engineering Macrophage‐Derived Exosome to Deliver Pirfenidone: A Novel Approach to Combat Silicotic Pulmonary Fibrosis

Engineering Macrophage‐Derived Exosome to Deliver Pirfenidone: A Novel Approach to Combat Silicotic Pulmonary Fibrosis

Pirfenidone microcrystals for pulmonary delivery: Regulation of the precipitation behavior in the supercooled droplet

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