Wu Chunfei, Bi Chuanlin, Kim Geun-Soo, Yang Zizhen, Li Shuao, Dai Tong, Wu Xiaoyu, Tan Jiaojiao, He Ningning, Li Shangyong
Medical School, Qingdao Huanghai University, Qingdao, China.
School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, China.
Sci Rep. 2025 Jan 10;15(1):1569. doi: 10.1038/s41598-024-84322-2.
Tofacitinib (Tof), a commercially available pan-Janus kinases inhibitor, is approved for the treatment of moderate to severe ulcerative colitis. However, its clinical application is limited due to dose-dependent systemic side effects. The present study aims to develop an efficient oral colon-targeted drug delivery systems using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a shell, with Tof loaded into a Bovine Serum Albumin (BSA) core, and improving it with chondroitin sulfate (Chs), thus constructing Tof@BSA-Chs-CP nanoparticles (NPs). Our results suggest that the pH-sensitive characteristics of the Pcn/Csn shell contribute to its capacity for attenuating absorption and systemic diffusion in the gastrointestinal tract, and exhibiting targeted localization at inflamed colonic sites in mice. Additionally, the gut microbiota-secreted polysaccharide-degrading enzyme acts as the triggering agent for Pcn/Csn shell degradation. In mice colitis models, we demonstrated that oral administration of Tof@BSA-Chs-CP NPs effectively ameliorated colitis and expedited its resolution by modulating the expression of pro-inflammatory cytokines and immune regulatory factors. Collectively, our synthetic NPs demonstrate the promising potential of Tof for the therapy of UC.
托法替布（Tof）是一种已上市的泛 Janus 激酶抑制剂，被批准用于治疗中度至重度溃疡性结肠炎。然而，由于其剂量依赖性的全身副作用，其临床应用受到限制。本研究旨在开发一种高效的口服结肠靶向给药系统，该系统以益生元果胶（Pcn）和壳聚糖（Csn）多糖为外壳，将托法替布负载于牛血清白蛋白（BSA）内核中，并用硫酸软骨素（Chs）对其进行改进，从而构建托法替布@BSA-Chs-CP 纳米颗粒（NPs）。我们的结果表明，Pcn/Csn 外壳的 pH 敏感特性有助于其在胃肠道中减弱吸收和全身扩散的能力，并在小鼠炎症性结肠部位表现出靶向定位。此外，肠道微生物群分泌的多糖降解酶充当 Pcn/Csn 外壳降解的触发剂。在小鼠结肠炎模型中，我们证明口服托法替布@BSA-Chs-CP NPs 可通过调节促炎细胞因子和免疫调节因子的表达有效改善结肠炎并加速其消退。总体而言，我们合成的 NPs 证明了托法替布治疗溃疡性结肠炎的潜在前景。
