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. 2020 Nov 13:13:569-576.
doi: 10.2147/CEG.S269568. eCollection 2020.

Barrier Effect of a New Topical Agent on Damaged Esophageal Mucosa: Experimental Study on an ex vivo Swine Model

Roberta Salaroli  1 , Domenico Ventrella  1 , Chiara Bernardini  1 , Alberto Elmi  1 , Augusta Zannoni  1   2 , Maria Laura Bacci  1   2 , Monica Forni  1   2 , Fiorella Calanni  3 , Antonella Ferrieri  4 , Fabio Baldi  5
Affiliations

Barrier Effect of a New Topical Agent on Damaged Esophageal Mucosa: Experimental Study on an ex vivo Swine Model

Roberta Salaroli et al. Clin Exp Gastroenterol. .

Abstract

Purpose: AL2106 is a new medical device based on a mixture of chondroitin sulphate in a xyloglucan and glycerol solution made to maximize its bioadhesive capability to the esophageal mucosa. The aim of the present study was twofold to evaluate the AL2106 protective effect on the esophageal mucosa when exposed to an acidic solution mimicking gastric reflux and to assess the resilience of this effect to saline washing.

Materials and methods: A porcine ex vivo model was used and the effects of the new medical device were compared to a sodium alginate suspension (SAS) already present on the market which was assumed as reference. Mucosal damage was induced in 19 porcine esophagi by perfusion with an acidic solution added with pepsin, and Evans blue dye (EBD) tissue uptake was used as an indicator of mucosal permeability. The EBD penetration, expressed as EBD µg/g of dry tissue, was assessed in specimens of untreated damaged mucosa and in specimens treated with AL2106 or SAS. The same evaluation was carried out after washing with normal saline.

Results: Both topical agents tested significantly reduced the EBD uptake by more than 60% (AL2106 8.4±4.5, SAS 3.6±2.7 vs control 23.2±13.1, p<0.01). The saline washing did not cause any significant reduction in the protective effect of AL2106 (8.6±5.9), while it significantly reduced that of SAS (5.9±4.3, p<0.05).

Conclusion: The new AL2106 medical device showed a good barrier effect against a reflux-like damaging solution and preserved this effect after the mucosal washing test, thus suggesting its possible relevance for the treatment of gastroesophageal reflux disease.

Keywords: EBD; Evans blue dye; GERD; animal model; bioadhesion; esophagus; gastroesophageal reflux disease.

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Conflict of interest statement

Alfasigma Spa was not involved in the study design, or in the collection, analysis and interpretation of the data. The views expressed in this article are the personal views of the authors and were not influenced by Alfasigma in any way. Alfasigma has agreed with the decision to submit this article for publication. Fiorella Calanni and Antonella Ferrieri are employees of Alfasigma. Maria Laura Bacci reports grants from Alfasigma during the conduct of the study. Fabio Baldi reports personal fees from Alfasigma during the conduct of the study. The authors report no other potential conflicts of interest for this work.

Figures

Figure 1
Figure 1
Porcine esophagus ex vivo model. An esophagus ablated of its adventitial and muscular layers (A) An esophagus ablated of the lower sphincters, pinned to the support, attached to a perfusion pump, and placed in the thermostatic hood (B).
Figure 2
Figure 2
Design of the study. Mucosal sampling and sequence of treatments after perfusion with the damaging solution. Six samples were taken from each esophagus. One served as epifluorescence control (CTR), one was stained with Evans blue dye (EBD) immediately while the others were treated with topical agents and stained with EBD, preceded or not by washing with saline.
Figure 3
Figure 3
The quantity of Evans blue dye (EBD) (µg/g) in the damaged mucosa treated with AL2106 and SAS. The data, expressed as a column chart, represent the mean ± standard deviation (SD) (vertical bars). EBD values in µg/g of dry tissue; Paired and unpaired Student’s t-test (parametric data).
Figure 4
Figure 4
The quantity of Evans blue dye (EBD) (µg/g) in the damaged mucosa treated with AL2106 and sodium alginate suspension (SAS) expressed as the difference in reduction versus the controls. Higher values indicate a greater reduction in EBD absorption. The data, expressed as a column chart, represent the mean ± standard deviation (SD) (vertical bars). Paired and unpaired Student’s t-test (parametric data).
Figure 5
Figure 5
Evans blue dye (EBD) mucosal penetration indicated by epifluorescence microscopy: Control sample (damaged mucosa, not treated with any topical agents and not stained with EBD) showed a very high orange background. Arrows point at EBD-related signal. (A1) An EBD-related signal was present in all layers of the multilayered squamous epithelium in the sample not treated with topical agents but stained with EBD. (A2) In the fragment treated with AL2106, the background signal was very high, but the EBD-related signal was restricted to some superficial epithelium layers. (B1) After washing, a small quantity of EBD penetrated the esophageal mucosa and submucosa. (B2) In the fragments treated with the sodium alginate suspension (SAS), the dye was present in only a few layers of the epithelium. (C1) Washing in saline partially restored the ability of EBD to penetrate the esophageal mucosa and submucosa. (C2) (bars: 200µm).
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References

    1. Klenzak S, Danelisen I, Brannan GD, Holland MA, van Tilburg MA. Management of gastroesophageal reflux disease: patient and physician communication challenges and shared decision making. World J Clin Cases. 2018;6(15):892–900. doi:10.12998/wjcc.v6.i15.892 - DOI - PMC - PubMed
    1. Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012;61(9):1340–1354. - PubMed
    1. Baldi F. PPI-refractory GERD: an intriguing, probably overestimated, phenomenon. Curr Gastroenterol Rep. 2015;17(7):25. doi:10.1007/s11894-015-0451-3 - DOI - PubMed
    1. Partial symptom‐response to proton pump inhibitors in patients with non‐erosive reflux disease or reflux oesophagitis – a post hoc analysis of 5796 patients - Bytzer - 2012 - Alimentary Pharmacology & Therapeutics - Wiley Online Library [Internet]. [cited April 23, 2020] Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12007. Accessed November4, 2020. - DOI - PubMed
    1. Topical protection of human esophageal mucosal integrity. American journal of physiology-gastrointestinal and liver physiology [Internet]. [cited April 23, 2020] Available from: https://journals.physiology.org/doi/full/10.1152/ajpgi.00424.2014. Accessed November4, 2020. - DOI - PubMed