Gastro-esophageal reflux disease (GERD) represents a common condition affecting millions of people worldwide with a global prevalence of almost 15% (Nirwan et al. 2020), reaching values higher than 21% in Europe (Eusebi et al. 2018) and 28% in USA (El Serag et al. 2014).
The disruption of the physiological barrier of the esophageal mucosa due to the acid refluxate represents the basis of GERD pathogenesis. Depending on the frequency of the reflux episodes, volume, composition of the refluxed contents (i.e. acidic and non-acidic) and the contact time with the esophageal mucosa, structural and functional damages to the epithelium may occur (De Hertog et al. 2006). As a result, these histopathological alterations often cause troublesome symptoms such as heartburn, regurgitation, chest pain and difficulty swallowing.
Treatment for GERD is generally targeted for gastric acid neutralization, suppression of gastric acid production and/or secretion and minimizing the exposure of the esophagus to refluxate. Among the products available in the OTC and medical device market the most popular are known as raft-forming anti-reflux preparations and act by forming a raft on the gastric content surface thus preventing it from flowing back into the esophagus.
RefluG™ Isorepair is a new patented medical device (class IIa) designed to reduce gastroesophageal reflux symptoms through an innovative mechanical mode of action. In particular, it coats and protects the esophageal mucosa sustaining the physiological healing process of damaged epithelium. The mucoadhesive, protective and regenerative effects of RefluG™ Isorepair against esophageal mucosal damage were assessed in different in vitro and ex vivo models by the Department of Life Sciences of Trieste University (Agostinis et al. 2020).
Study description
CP-A and COLO-680N immortalized human esophageal cells were used as in vitro GERD models to evaluate the mucoadhesive and reparative properties of the investigational product (RefluG™ Isorepair) in comparison to a viscous control. A medium containing a bile salts cocktail with pepsin (BSC) was used to simulate the irritant effect of the gastric content.
Binding assay was aimed to evaluate the mucoadhesive properties of RefluG™ Isorepair. Cell monolayers were exposed to both RefluG™ Isorepair and control stained with 0.1% bromophenol blue for different periods (ranging from 1 to 180 minutes). The bound product was evaluated and quantified by an ELISA reader.
The results showed that RefluG™ Isorepair was able to bind the esophageal epithelial cells very quickly and better compared to the control (fig. 1 *p<0.05). Moreover, after several washings, RefluG™ Isorepair remained bound up to 60 minutes. The protective layer formed by RefluG™ isorepair leads to significant improvement of cell permeability and tight junction dysfunction induced by the irritant medium.
Figure 1.
A mechanical wound (i.e. scratch wound healing assay) in a monolayer of esophageal epithelial cells was performed to assess the re-epithelization action of RefluG™ Isorepair. Cells were incubated with BSC and then, after 2 hours, were treated with either RefluG™ Isorepair or control and observed up to 24 hours using a time lapse inverted microscope.
At the end of the observational period, RefluG™ Isorepair was found to significantly (p<0.05) increase wound healing in BSC-treated cells thus sustaining the physiological regenerative process of the damaged esophageal mucosa (fig. 2).
Figure 2.
Conclusions
Results from our preclinical study provide evidence that RefluG™ Isorepair medical device is able to bind to human esophageal cells, improve the integrity of the mucosal barrier protecting the esophagus against the damaging effects of bile salts and pepsin, and at the same time to sustain the healing process in case of epithelial injuries.
Such actions are due to the synergic composition of RefluG™ Isorepair, a liquid gel preparation containing hyaluronic acid, rice extract, and amino acids dispersed in an effective bioadhesive polymer matrix which retains the functional components to the target site of action i.e. esophageal mucosa. The protective barrier effect and its unique non-systemic physical mode of action makes RefluG™ Isorepair innovative and different from products and medical devices used for the same intended use (GERD symptoms relief). The clinical effectiveness and safety of RefluG™ Isorepair has been confirmed by a double-blind, placebo-controlled clinical study (Ribaldone et al. 2021) while a new multicentric study is on-going to determine its efficacy in combination with Proton Pump Inhibitor (PPI), the most commonly prescribed treatment in subjects suffering from GERD.
For more information, click this link and watch the RefluG™ Isorepair video.
References
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- Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford AC. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut 2018;67:430–400.
- El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014; 63(6):871-80.
- De Hertogh G, Ectors N, Van Eyken P, Geboes K. Review article: the nature of oesophageal injury in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2006; 24 (Suppl. 2): 17-26.
- Agostinis C, Bossi F, Mangogna A, Balduit A, Pacor M, Giacomello E, Belmonte B, Greco D, Rodolico V, Voinovich D, De Seta F, Ricci G, Bulla R. Protective and regenerative effects of a novel medical device against esophageal mucosal damage using in vitro and ex vivo models. Biomed Pharmacother 2020; 131:110752.
- Ribaldone DG, Rajesh P, Chandradhara D, Astegiano M, Pellicano R. A randomized, double-blind, placebo-controlled pilot study to evaluate the efficacy and tolerability of a novel oral bioadhesive formulation for the treatment of nonerosive reflux disease-related symptoms. Eur J Gastroenterol Hepatol. 2021; 32(2):163-170.