Mucoprotective effect of a galactomannan- and hyaluronic-based medical device in a reconstructed human esophageal epithelium.

Abstract

Gastroesophageal reflux disease (GERD) is a common disorder characterized by troublesome symptoms (classically, heartburn and regurgitation). Repeated or prolonged exposure to gastric contents may cause irritation and inflammation of the esophageal mucosa. RefluG™ is a medical device conceived to form a physical barrier on contact with gastric contents, neutralize stomach acid excess, and elicit a mucoprotective effect. The aim of the current study was to investigate the mucoprotective potential of RefluG™ (IHS, Biofarma Group, Lissone, Italy) in a simulated reflux model. A 3D reconstructed human esophageal epithelium was treated with RefluG™ or sodium alginate (reference sample) or saline solution (negative control) or acid solution (positive control) in a prevention or treatment approach. Histological protection, mucoprotective and barrier effects were evaluated. Preservation of epithelial permeability was determined by measuring the transepithelial electrical resistance (TEER) and the Lucifer yellow assay. Interleukin (IL)-6 levels were determined as indicator of the ability of RefluG™ to attenuate and/or prevent esophageal irritation. RefluG™ was found to better preserve tissue morphology while the epithelial membranes showed higher integrity, as revealed by TEER analysis, compared to the other samples. Luciferin passage was significantly reduced following RefluG™ treatment with respect to other treatment groups. Moreover, after acid insult, RefluG™ treatment significantly decreased IL-6 release into the culture media compared to the reference sample or positive control. These results provide experimental evidence on the efficacy of RefluG™ in preserving the integrity of the esophageal barrier and support data regarding the symptomatic relief observed in patients with GERD receiving RefluG™ as monotherapy.