Inhaled PAMAM-based nano-formulation prolonged lung retention for alleviating pulmonary inflammation of COPD

Inhaled PAMAM-based nano-formulation prolonged lung retention for alleviating pulmonary inflammation of COPD

Chronic obstructive pulmonary disease (COPD) stands as a predominant respiratory disorder intricately linked with respiratory tract microorganisms and their metabolites. Indole acetic acid (IAA), a derivative of tryptophan produced by Lactobacillus salivarius, possesses notable anti-inflammatory pro...

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Bibliographic Details
Main Authors: Chen Wang, Xiao-yan Hu, Ri Ji, Yi-fan Lu, Xiang Shen, Zhang Wang, Fei Wang, Guo-chao Shi, Yun Feng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
Subjects:
G4-PAMAM nanoparticle
Nanocomposite
Drug delivery
Chronic obstructive pulmonary disease
Indole-3-acetic acid
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425004053
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Summary:Chronic obstructive pulmonary disease (COPD) stands as a predominant respiratory disorder intricately linked with respiratory tract microorganisms and their metabolites. Indole acetic acid (IAA), a derivative of tryptophan produced by Lactobacillus salivarius, possesses notable anti-inflammatory properties. However, the short retention time of the drug in lung still remains a vital obstacle leading to a poor bioavailability. In this study, we innovatively engineer a nano-composite by coupling IAA with generation 4 polyamidoamine (G4 PAMAM) dendrimer to form G4-IAA nano-complex through host-guest interaction. G4-IAA shows significantly improved solubility of IAA and thus enhances its bioavailability. This G4-IAA complex facilitates direct aerosol-based pulmonary administration by inhaled strategy, exhibiting enhanced absorption by respiratory epithelial cells and prolonged lung retention. Our experimental findings reveal that inhalation therapy employing the G4-IAA complex mitigates inflammatory stress and augments pulmonary function in COPD murine models. Single-cell sequencing reveals macrophages may contribute to the functional shifts by G4-IAA, promoting an anti-inflammatory phenotype characteristic of M2 polarization. This research introduces a promising therapeutic strategy, offering improved symptomatic relief and reduced risk of acute exacerbations for individuals afflicted with COPD.
ISSN:2590-0064

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