School of Environmental Engineering, Wuxi University, Wuxi 214105, P. R. China.
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, P. R. China.
J Mater Chem B. 2023 Dec 6;11(47):11228-11234. doi: 10.1039/d3tb02128a.
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 Zr enabled tracking localization with positron emission tomography (PET) imaging. Rectal administration of Zr-INF@PPNP led to colon delivery with remarkably reduced systemic exposure intravenous INF revealed by non-invasive PET imaging. Zr-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.
炎症性肠病（IBD），如克罗恩病和溃疡性结肠炎，涉及慢性胃肠道炎症。促炎细胞因子肿瘤坏死因子-α（TNF-α）驱动 IBD 的发病机制。使用单克隆抗体（mAb）如英夫利昔单抗（INF）的抗 TNF-α 疗法有助于治疗 IBD，但存在局限性。我们开发了载有抗炎 mAb INF 的炎症靶向多酚-泊洛沙姆纳米粒子（INF@PPNP），作为一种新型的 IBD 治疗方法。表征表明，INF@PPNP 具有良好的稳定性和纯度。用 Zr 对 INF@PPNP 进行放射性标记，使正电子发射断层扫描（PET）成像能够跟踪定位。Zr-INF@PPNP 的直肠给药导致结肠给药，显著减少了通过非侵入性 PET 成像显示的系统暴露。Zr-INF@PPNP 在炎症病灶处的保留表明 INF@PPNP 的作用延长。INF@PPNP 直肠给药与静脉注射 INF 达到相似的抗炎效果，显示出很高的治疗潜力。我们的研究结果支持使用基于纳米粒子的直肠给药进行局部药物递送，延长药物活性并最小化系统暴露，最终为治疗 IBD 提供一种有效的方法。
