Hyaluronic acid and chondroitin sulfate-based medical devices: formulations, esophageal mucosal protection, and their place in the management of GERD.

Gastroesophageal reflux disease (GERD) remains a challenging condition, even in the third millennium. For much of the past century, Schwartz's dictum-"No acid, no ulcer"-has shaped our approach to acid-related diseases, making acid suppression the cornerstone of therapy. Proton pump inhibitors (PPIs) are widely regarded as the standard treatment for GERD. However, they provide only symptomatic relief and do not address the underlying disease. Moreover, nearly 50% of patients experience limited or no response to PPIs in clinical practice. Recent advances in understanding GERD's pathophysiology, particularly the role of impaired mucosal integrity, have led to innovative therapeutic strategies. Among these, medical devices designed to prevent reflux or coat the esophageal mucosa and form a stable protective barrier represent a significant breakthrough. Esophageal mucosal protection is emerging as a promising approach, especially for patients who do not respond adequately to PPIs. While mucosal-protective agents such as sucralfate and irsogladine have long been available, their formulations have not been well-suited for esophageal protection. The rapid transit time of liquids through the esophagus (typically just a few seconds, even in a supine position) limits the duration of contact between active ingredients and the mucosa. However, hyaluronic acid and chondroitin sulfate-based medical devices have revolutionized the field by enabling active ingredients to adhere to the esophageal lining, ensuring prolonged contact and enhanced protection. Further advancements have led to the development of three distinct formulations (Esoxx™ One, Esoxx Defence, and Esoxx Protection), incorporating additional components, that is, Poloxamer 407, aluminum hydroxide, or natural remedies such as