Microfluidic synthesis of HAMA-Loaded quercetin reverses epithelial-mesenchymal transition in chronic bronchial asthma by modulating macrophage polarization

Objectives To investigate the potential of hyaluronic acid (HAMA) loaded with quercetin (QT) as named (HAMA@QT) nanoparticles, synthesized via microfluidic technology, to reverse epithelial-mesenchymal transition (EMT) in chronic bronchial asthma by modulating macrophage polarization. Methods HAMA@QT nanoparticles were synthesized by encapsulating quercetin (QT) within a HAMA matrix using a microfluidic technique. The nanoparticles were characterized by various techniques, including scanning electron microscopy (SEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). HAMA@QT in vitro effects were assessed in BEAS-2B cells, while HAMA@QT in vivo therapeutic potential was evaluated in a chronic allergic asthma mouse model. Various assays such as wound healing, Transwell migration, and immunofluorescence were conducted to analyze EMT reversal, macrophage polarization, and cell viability. Additionally, histological and biochemical analyses were performed to assess pulmonary inflammation and fibrosis in the mouse model. Results HAMA@QT nanoparticles exhibited successful encapsulation of quercetin, with high encapsulation efficiency (81.4%) and a sustained drug release profile. In vitro, HAMA@QT significantly reversed LPS-induced EMT in BEAS-2B cells, as evidenced by enhanced migration, increased E-cadherin expression, and decreased Vimentin and α-SMA levels. In vivo, HAMA@QT treatment reduced airway inflammation, mucus secretion, and fibrosis in an asthma mouse model. Furthermore, HAMA@QT nanoparticles promoted M2 macrophage polarization, indicated by increased CD206 expression and reduced iNOS levels, while alleviating inflammation. The nanoparticles effectively reversed EMT in lung tissue by restoring E-cadherin expression and reducing Vimentin and α-SMA in the treated animals. Conclusion HAMA@QT nanoparticles reverse EMT and regulate macrophage polarization in chronic bronchial asthma, alleviate airway inflammation and fibrosis, and represent a promising therapeutic strategy for chronic asthma treatment.