A Colon-Targeted Oral Nanosystem Disrupts the Inflammatory Loop in Enteric Glia to Alleviate Ulcerative Colitis

Area of Science:

• Neurogastroenterology
• Nanomedicine
• Immunology

Background:

• Enteric glial cells (EGCs) in the enteric nervous system regulate gut inflammation.
• Hyperactive EGCs release S100 calcium-binding protein B (S100B), initiating a proinflammatory cascade involving reactive oxygen species (ROS).
• This creates a detrimental feedback loop exacerbating gut inflammation and conditions like ulcerative colitis.

Purpose of the Study:

• To develop a targeted nanomedicine to inhibit S100B and break the inflammatory cycle in EGCs.
• To evaluate the efficacy of the developed nanoneedle system in ameliorating ulcerative colitis.

Main Methods:

• Development of a pentamidine (PTM)-loaded olsalazine-based nanoneedle (Zn2(Olsa)/PTM) as a S100B inhibitor.
• Coating the nanoneedle with Eudragit L100-55 for colon-targeted delivery (ZOP@Eud).
• Assessment of ZOP@Eud's effects on S100B and ROS levels in EGCs and in a murine model of ulcerative colitis.

Main Results:

• Zn2(Olsa)/PTM demonstrated enhanced cytocompatibility and reduced S100B and ROS production in EGCs.
• Oral administration of ZOP@Eud significantly reduced disease severity in the ulcerative colitis model.
• Treatment restored mucosal barrier integrity and immune homeostasis, evidenced by increased tight junction proteins and decreased proinflammatory markers.

Conclusions:

• Targeted nanosystems inhibiting EGC-mediated inflammation offer a promising therapeutic strategy for ulcerative colitis.
• ZOP@Eud effectively mitigates gut inflammation by targeting the S100B/ROS feedback loop.
• This approach highlights the potential of nanomedicine in neurogastroenterology for treating inflammatory bowel diseases.