Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou 310003, China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Carbohydr Polym. 2021 Dec 1;273:118556. doi: 10.1016/j.carbpol.2021.118556. Epub 2021 Aug 14.
The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.
抗肿瘤坏死因子-α（anti-TNF-α）阻滞剂在治疗炎症性肠病（IBD）方面显示出了巨大的疗效。然而，由于对全身免疫反应的抑制作用降低以及对产生抗药物抗体的反应丧失，全身暴露于该药物会引起相当大的安全问题。因此，我们试图设计一种针对口服给予抗 TNF-α 抗体的靶向载体系统，用于治疗 IBD。在本研究中，我们开发了一种基于壳聚糖（CS）/羧甲基壳聚糖（CMC）和海藻酸钠（Alg）的负载英夫利昔单抗（IFX）的纳米-微米载药系统，可保护 IFX 免受胃肠道恶劣环境的影响，并将药物靶向递送至发炎的肠道。体内研究表明，负载 IFX 的纳米-微米载体可以通过改善炎症和维持肠道上皮屏障来缓解结肠炎。
