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

Gabriele De Rubis; Keshav Raj Paudel; Gang Liu; Vipul Agarwal; Ronan MacLoughlin; Terezinha de Jesus Andreoli Pinto; Sachin Kumar Singh; Jon Adams; Srinivas Nammi; Dinesh Kumar Chellappan; Brian Gregory George Oliver; Philip Michael Hansbro; Kamal Dua

doi:10.1016/j.tiv.2023.105660

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

Toxicol In Vitro. 2023 Oct:92:105660. doi: 10.1016/j.tiv.2023.105660. Epub 2023 Aug 15.

Affiliations

¹ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
² Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia.
³ Cluster for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Aerogen, IDA Business Park, H91 HE94 Galway, Connacht, Ireland; School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Leinster, Ireland; School of Pharmacy & Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Leinster, Ireland.
⁵ Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
⁶ Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
⁷ Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
⁸ School of Science, Western Sydney University, Penrith, NSW 2751, Australia.
⁹ Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
¹⁰ Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
¹¹ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India. Electronic address: kamal.dua@uts.edu.au.

PMID: 37591407
DOI: 10.1016/j.tiv.2023.105660

Abstract

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-β (TGF-β), 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-β 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-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β 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-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-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.

Keywords: Airway remodelling; Asthma; Berberine; COPD; Liquid crystalline nanoparticles; Lung cancer; Phytoceuticals; TGF-β.

MeSH terms

Airway Remodeling
Antioxidants
Berberine* / pharmacology
Cell Proliferation
Epithelial Cells
Humans

Substances

Berberine
Antioxidants