Wu Wen, Zhang Jian, Qu Xiao, Chen Ting, Li Jinming, Yang Yongzhi, Chen Lifeng, Hoover Alex, Guo Fanying, Kong Cheng, Bao Bingkun, Lin Qiuning, Zhou Mengxin, Zhu Linyong, Wu Xiaoyang, Ma Yanlei
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Shanghai, 200032, China.
Ben May Department for Cancer Research, University of Chicago, GCIS W408B, 929 E 57th Street, Chicago, IL, 60637, USA.
Adv Sci (Weinh). 2025 Mar;12(12):e2404836. doi: 10.1002/advs.202404836. Epub 2025 Feb 3.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease. UC treatments are limited by significant adverse effects associated with non-specific drug delivery, such as systematic inhibition of the host immune system. Endoscopic delivery of a synthetic hydrogel material with biocompatible gelation that can efficiently cover irregular tissue surfaces provides an effective approach for targeted drug delivery at the gastrointestinal (GI) tract. An ideal integration of synthetic material with intestinal epithelium entails an integrated and preferable chemically bonded interface between the hydrogel and mucosal surface. In this study, a photo-triggered coupling reaction is leveraged as the crosslinking platform to develop a mucosal-adhesive hydrogel, which is compatible with endoscope-directed drug delivery for UC treatment. The results demonstrated superior spatiotemporal specificity and drug pharmacokinetics with this delivery system in vivo. Delivery of different drugs with the hydrogel leads to greatly enhanced therapeutic efficacy and significantly reduced systemic drug exposure with rat colitis models. The study presents a strategy for targeted and persistent drug delivery for UC treatment.
溃疡性结肠炎（UC）是一种慢性炎症性肠病。UC的治疗受到与非特异性药物递送相关的显著不良反应的限制，例如对宿主免疫系统的系统性抑制。通过内镜递送具有生物相容性凝胶化且能有效覆盖不规则组织表面的合成水凝胶材料，为胃肠道（GI）的靶向药物递送提供了一种有效方法。合成材料与肠上皮的理想整合需要水凝胶与粘膜表面之间形成整合且更优的化学键合界面。在本研究中，利用光触发偶联反应作为交联平台来开发一种粘膜粘附水凝胶，该水凝胶与内镜引导的药物递送兼容，用于UC治疗。结果表明，该递送系统在体内具有优异的时空特异性和药物药代动力学。在大鼠结肠炎模型中，用水凝胶递送不同药物可显著提高治疗效果，并显著减少全身药物暴露。该研究提出了一种用于UC治疗的靶向和持续药物递送策略。
