Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, People's Republic of China.
School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, Jiangsu, People's Republic of China.
Int Immunopharmacol. 2024 Sep 30;139:112661. doi: 10.1016/j.intimp.2024.112661. Epub 2024 Jul 14.
The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2. However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier. ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1β. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.
5-氨基水杨酸（5-ASA）是治疗溃疡性结肠炎（UC）的一线治疗药物，但由于其口服生物利用度较低，治疗效果有限。本研究采用 Eudragit S100 包衣的氧化铁壳聚糖纳米复合材料（ES-IOCS/5-ASA）开发了一种 5-ASA 口服递药系统，以解决这一问题。根据体外药物释放研究，ES-IOCS/5-ASA 在 pH 值为 1.2 的模拟胃液中仅释放少量药物，但在 pH 值为 7.5 的介质中则迅速且完全释放。载有 5-ASA 的氧化铁壳聚糖纳米复合材料（IOCS/5-ASA）可被 NCM460 细胞有效摄取，并表现出比游离 5-ASA 更好的抗炎效果。同时，IOCS/5-ASA 改善了 DSS 诱导的 NCM460 细胞中的屏障损伤。采用葡聚糖硫酸钠（DSS）诱导的结肠炎动物模型评估 ES-IOCS/5-ASA 口服给药的治疗效果。ES-IOCS/5-ASA 显著缓解 DSS 诱导的结肠炎，并增强肠道上皮屏障的完整性。ES-IOCS/5-ASA 还降低了 NLRP3、ASC 和 IL-1β的表达。此外，氧化铁纳米颗粒作为纳米酶可缓解炎症。综上所述，本研究表明 ES-IOCS/5-ASA 通过改善肠道屏障功能和抑制 NLRP3 炎性小体表达，对 DSS 诱导的结肠炎发挥抗炎作用，为 UC 的治疗提供了一种可行的治疗选择。
