Oridonin-Loaded PDA@Gel@GO Nanocapsules Modulate NLRP3 and Epithelial Repair in Colitis.

Area of Science:

• Gastroenterology and Immunology
• Nanomedicine and Drug Delivery
• Natural Product Chemistry

Background:

• Ulcerative colitis (UC) involves chronic inflammation and barrier dysfunction, often linked to NLRP3 inflammasome activation.
• Current oral therapies for UC struggle to simultaneously reduce inflammation and heal the gut lining.
• Oridonin, a natural compound, shows anti-inflammatory potential but requires effective delivery.

Purpose of the Study:

• To develop an orally administrable, colon-targeted nanomicrocapsule system (PDA@Gel@GO) for delivering oridonin.
• To evaluate the therapeutic efficacy of PDA@Gel@GO in a dextran sulfate sodium (DSS)-induced UC mouse model.
• To elucidate the mechanisms underlying PDA@Gel@GO's anti-inflammatory and mucosal repair effects.

Main Methods:

• Fabrication of PDA@Gel@GO by encapsulating oridonin nanomicelles within gelatin microspheres and coating with polydopamine.
• Administration of PDA@Gel@GO to DSS-induced UC mice and assessment of colon tissue accumulation.
• Evaluation of therapeutic effects using disease activity index, body weight, colon length, and molecular markers of NLRP3 inflammasome, oxidative stress, and barrier proteins.
• Transcriptomic analysis to identify affected gene pathways.

Main Results:

• PDA@Gel@GO demonstrated preferential accumulation in inflamed colonic tissue.
• Treatment significantly improved UC symptoms, including body weight loss and colon damage.
• PDA@Gel@GO suppressed NLRP3 inflammasome activation, reduced oxidative stress, and restored intestinal barrier integrity.
• Transcriptomics revealed enhanced epithelial regeneration, cell cycle, and DNA repair pathways.

Conclusions:

• The PDA@Gel@GO system provides effective colon-targeted delivery of oridonin for UC treatment.
• This platform integrates anti-inflammatory and tissue-protective actions, offering a promising strategy for precision UC therapy.
• The study highlights the potential of macrophage-targeted nanomaterials for managing inflammatory bowel diseases.