Huo De-Yang, Li Yan-Fei, Song Ling-Jie, Zhang Wen-Xin, Li Xin-Dian, Zhang Jing, Ren Shen, Wang Zi, Li Wei
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China.
Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
Adv Healthc Mater. 2025 Mar;14(6):e2404122. doi: 10.1002/adhm.202404122. Epub 2025 Jan 10.
Natural plant-derived polysaccharides exhibit substantial potential for treating ulcerative colitis (UC) owing to their anti-inflammatory and antioxidant properties and favorable safety profiles. However, their practical application faces several challenges, including structural instability in gastric acid, imprecise targeting of inflamed regions, and limited intestinal retention times. To address these limitations, pH-responsive, colon-targeting microspheres (pWGPAC MSs) are developed for delivering phosphorylated wild ginseng polysaccharides (pWGP) to alleviate UC. These pWGPAC MSs are fabricated by incorporating pWGP into calcium-crosslinked alginate microspheres with subsequent chitosan surface modification to enhance mucosal adhesion. These pWGPAC MSs demonstrated exceptional stability under acidic conditions while enabling targeted release in the colon. In a mouse model of UC, the pWGPAC MSs effectively mitigated mucosal injury, attenuated inflammation, and restored intestinal barrier function. Further mechanistic investigations revealed that these pWGPAC MSs modulated the TLR4/MYD88 signaling pathway and promoted M2 macrophage polarization. Integrated microbiome and metabolome analyses demonstrated that these pWGPAC MSs regulated the gut microbiota composition and decreased pro-inflammatory metabolite levels. In addition, these microspheres demonstrated promising safety profiles. Collectively, these findings establish pWGPAC MSs as a promising therapeutic strategy for the treatment of UC and provide a solid foundation for future clinical applications.
天然植物来源的多糖由于其抗炎、抗氧化特性以及良好的安全性，在治疗溃疡性结肠炎（UC）方面具有巨大潜力。然而，它们的实际应用面临一些挑战，包括在胃酸中结构不稳定、对炎症区域的靶向不精确以及肠道保留时间有限。为了解决这些限制，开发了pH响应性结肠靶向微球（pWGPAC MSs），用于递送磷酸化野生人参多糖（pWGP）以缓解UC。这些pWGPAC MSs是通过将pWGP掺入钙交联藻酸盐微球中，随后进行壳聚糖表面修饰以增强粘膜粘附来制备的。这些pWGPAC MSs在酸性条件下表现出优异的稳定性，同时能够在结肠中实现靶向释放。在UC小鼠模型中，pWGPAC MSs有效减轻了粘膜损伤，减轻了炎症，并恢复了肠道屏障功能。进一步的机制研究表明，这些pWGPAC MSs调节了TLR4/MYD88信号通路并促进了M2巨噬细胞极化。综合微生物组和代谢组分析表明，这些pWGPAC MSs调节了肠道微生物群组成并降低了促炎代谢物水平。此外，这些微球表现出良好的安全性。总体而言，这些发现确立了pWGPAC MSs作为一种有前途的UC治疗策略，并为未来的临床应用提供了坚实的基础。
