An inflammation-responsive therapeutic gel for precise microbiota modulation in colitis.

Area of Science:

• Biomaterials Science
• Gastroenterology
• Microbiome Research

Background:

• Microbiome dysbiosis is central to inflammatory bowel disease (IBD), necessitating novel therapeutic strategies.
• Current IBD treatments face challenges with gastrointestinal instability and non-specific toxicity, limiting efficacy and potentially worsening symptoms.

Purpose of the Study:

• To develop a novel calcium phosphotungstate gel (CPW) for targeted IBD therapy.
• To engineer CPW for specific disintegration in response to inflammatory biomarkers and controlled release of therapeutic agents.
• To evaluate CPW's efficacy in modulating the gut microbiome and reducing inflammation in a preclinical IBD model.

Main Methods:

• Fabrication of a stable, nanofiber-based calcium phosphotungstate gel (CPW) resistant to gastrointestinal conditions.
• Demonstration of CPW's calprotectin-triggered disintegration and tungsten ion release.
• Assessment of tungsten ion's selective antimicrobial activity against nitrate-dependent pathogens.
• Evaluation of CPW as a protective carrier for various therapeutics, enabling targeted release at inflamed sites.
• In vivo testing of dexamethasone-loaded CPW (DEX@CPW) in DSS-induced colitis mice.

Main Results:

• CPW nanofibers form a stable 3D network, intact in gastrointestinal fluid for over 24 hours.
• CPW specifically disintegrates in response to calprotectin, releasing tungsten ions that selectively inhibit pathogens.
• CPW protected diverse therapeutics, achieving >70% release at inflamed sites.
• DEX@CPW treatment in mice significantly improved colon length, reduced pro-inflammatory cytokines, and restored beneficial microbiota.
• CPW demonstrated superior intestinal retention and reduced systemic tungsten exposure.

Conclusions:

• CPW serves as a dual-function platform for pathogen-selective metallotherapy and inflammation-triggered drug delivery.
• This approach offers precise microbiome modulation and inflammation amelioration for IBD.
• CPW represents a promising clinical strategy for managing inflammatory bowel disease.