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An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease.

ABSTRACT: Inflammatory bowel disease (IBD) is a chronic and refractory condition characterized by disrupted epithelial barrier, dysregulated immune balance, and altered gut microbiota. Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD. Herein, we developed a combination of olsalazine (Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation. The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages. The composite of nanoneedles and inulin gel (Cu₂(Olsa)/Gel) displayed a macroporous structure, improved bio-adhesion, and enhanced colon retention after oral administration. Mechanistically, the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies, resulting in significant alleviation of colitis in three animal models of IBD. Furthermore, analysis of gut microbiota revealed that Cu₂(Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria. Overall, this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy, offering an efficient approach to restore intestinal homeostasis.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC10658185 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease.

Zhang Zhuangzhuang Z Pan Yang Y Guo Zhaoyuan Z Fan Xi X Pan Qingqing Q Gao Wenxia W Luo Kui K Pu Yuji Y He Bin B

Bioactive materials 20231108

Inflammatory bowel disease (IBD) is a chronic and refractory condition characterized by disrupted epithelial barrier, dysregulated immune balance, and altered gut microbiota. Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD. Herein, we developed a combination of olsalazine (Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation. The Olsa-derived nanoneedles exhibited react ...[more]

PMID: 38024237

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Project description:BackgroundDue to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon.ResultsIn this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment.ConclusionsIt's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.

Dataset Information

An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease.

Publications

An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease.

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