Rectal delivery of 89Zr-labeled infliximab-loaded nanoparticles enables PET imaging-guided localized therapy of inflammatory bowel disease
Literature Information
Yeli Fan, Xinyu Wang, Ge Yan, Hongfang Gao, Min Yang
Inflammatory bowel diseases (IBDs) like Crohn's disease and ulcerative colitis involve chronic gastrointestinal inflammation. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) drives IBD pathogenesis. Anti-TNF-α therapies using monoclonal antibodies (mAbs) like infliximab (INF) help treat IBD but have limitations. We developed inflammation-targeting polyphenol–poloxamer nanoparticles loaded with the anti-inflammatory mAb INF (INF@PPNP) as a novel IBD therapy. Characterization showed that INF@PPNP had favorable stability and purity. Radiolabeling INF@PPNP with 89Zr enabled tracking localization with positron emission tomography (PET) imaging. Rectal administration of 89Zr-INF@PPNP led to colon delivery with remarkably reduced systemic exposure versus intravenous INF revealed by non-invasive PET imaging. 89Zr-INF@PPNP retention at inflamed foci indicated prolonged INF@PPNP action. INF@PPNP rectally achieved similar anti-inflammatory effects as intravenously injected INF, demonstrating the high therapeutic potential. Our findings support the use of nanoparticle-based rectal administration for localized drug delivery, prolonging drug activity and minimizing systemic exposure, ultimately offering an effective approach for treating IBD.
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