Orally Administrable H2S-Scavenging Metal-Organic Framework Prepared by Co-Flow Microfluidics for Comprehensive Restoration of Intestinal Milieu

Intestinal milieu disorders are strongly related to the occurrence of inflammatory bowel diseases (IBDs), which results from mucosa destruction, epithelium disruption, and tight junction (TJ) proteins loss. Excess of H2S in the intestinal milieu produced by the sulfate-reducing bacteria metabolism contributes to development of IBDs via epithelial barrier breakdown. Conventional interventions, such as surgery and anti-inflammatory medications, are considered not completely effective because of frequent recurrence and other complications. Herein, a novel oral delivery system, a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based polymer-coated Zr-based metal-organic framework (UiO-66) with a Cu-x-rhodamine B (CR) probe (hereinafter referred to as HUR), is produced via a co-flow microfluidic approach with the ability to reduce H2S levels, thus restoring the intestinal lumen milieu. HPMCAS serves as an enteric coating that exposes UiO-66@CR at the pH of the intestine but not the acidic pH of the stomach. The synthesized HUR exhibits notable therapeutic efficacy, including mucosa recovery, epithelium integrity restoration, and TJ proteins upregulation via H2S scavenging to protect against intestinal barrier damage and microbiome dysbiosis. Thus, HUR is verified to be a promising theranostic platform able to decrease the H2S content for intestinal milieu disorder treatment. The presented study therefore opens the door for further exploitation for IBDs therapy.

Automated summary

Intestinal milieu disorders are closely associated with the development of inflammatory bowel diseases (IBDs), which involve mucosa destruction, epithelium disruption, and loss of tight junction (TJ) proteins. An excess of H2S in the intestinal milieu produced by sulfate-reducing bacteria metabolism leads to breakdown of the epithelial barrier in IBDs. Conventional interventions for IBDs, such as surgery and anti-inflammatory medications, are not completely effective due to frequent recurrence and complications. In this study, a novel oral delivery system called HUR was developed, which consists of a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based polymer-coated UiO-66 metal-organic framework with a Cu-x-rhodamine B (CR) probe. HUR has the ability to reduce H2S levels and restore the intestinal lumen milieu, exhibiting therapeutic efficacy in terms of mucosa recovery, epithelium integrity restoration, and upregulation of TJ proteins.