Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-beta (TGF-beta), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-beta is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-beta-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-beta-induced migration, reducing the levels of proteins upregulated by TGF-beta including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-beta. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-beta. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-beta-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.

Automated summary

Airway remodelling, a common phenomenon in chronic respiratory diseases, is characterized by aberrant activation of epithelial repair, excessive extracellular matrix deposition, epithelial-to-mesenchymal transition, and airway obstruction. This study demonstrates the therapeutic efficacy of berberine-loaded liquid crystalline nanoparticles in inhibiting TGF-beta-induced remodelling features in human bronchial epithelial cells, supporting its potential application as a treatment strategy against chronic respiratory diseases.