Colon-targeted microbiota-modulating nanoparticles amplify azathioprine efficacy via gut microbiota axis remodeling in inflammatory bowel disease.

APZE nanoparticles improved oral bioavailability of azathioprine compared to AZA suspension in rats.

• APZE was constructed from pectin, Zein, and Eudragit S100 to encapsulate AZA
• The formulation enhanced cellular and intestinal uptake of AZA
• Oral bioavailability was improved compared to AZA suspension in rat pharmacokinetic studies
• Colon targeting ability and mucoadhesive properties prolonged colonic retention

APZE demonstrated superior colonic accumulation as measured by colon fluorescence intensity after oral administration of DiR-labeled formulation in rats.

• Colonic accumulation was quantified using AUC of colon fluorescence intensity
• DiR-labeled APZE formulation was used to track biodistribution in rats
• The colon-targeting ability was attributed to Eudragit S100, which is pH-responsive and releases contents in the colon
• Mucoadhesive properties of pectin contributed to prolonged colonic retention

APZE significantly reduced inflammation in DSS-induced IBD mice and repaired the intestinal barrier.

• Animal studies used a DSS-induced colitis mouse model
• APZE treatment significantly reduced inflammatory markers compared to controls
• Intestinal barrier repair was demonstrated in APZE-treated mice
• APZE exhibited significant therapeutic efficacy with good safety profile

APZE modulated gut microbiota composition and upregulated short-chain fatty acid levels in IBD mice.

• Gut microbiota remodeling was identified as a key mechanism of APZE therapeutic action
• Short-chain fatty acid levels were upregulated following APZE treatment
• The protective effect of APZE against colitis was described as largely microbiota-dependent
• The study framed the therapeutic mechanism as operating via a gut microbiota axis

Co-administration of APZE with commercially available Bifidobacterium attenuated colitis effectively and demonstrated excellent therapeutic effects and favorable safety.

• Bifidobacterium was used as a commercially available probiotic co-treatment
• The combination of APZE and Bifidobacterium improved intestinal barrier repair
• Co-administration improved colitis-related outcomes in the DSS-induced model
• The combination demonstrated favorable safety in the animal model