基于模板自组装法构建英夫利昔单抗纳米复合物及其口服治疗炎症性肠病研究

炎症性肠病（IBD）是一种病因不明的慢性非特异性肠道炎症性病变，治疗周期长、病情易反复，给患者的心理、工作和生活造成很大影响，且发病率逐年增高。英夫利昔单抗是目前国内唯一一个被批准用于治疗IBD的抗肿瘤坏死因子TNF-α单克隆抗体，临床上通常采用静脉滴注给药，这种给药方式在药物缺乏对靶部位的选择性作用下致使全身TNF-α均受到抑制，从而产生一系列不良反应。为此，本课题基于英夫利昔单抗口服给药这一设想，以透明质酸为载体材料，通过苯硼酸酯基团将英夫利昔单抗偶联至透明质酸分子主链，然后基于药物自身模板-分子自组装法形成纳米复合物，再予以交联固化制备具有IBD病变部位活性氧响应性释药的英夫利昔单抗口服纳米给药系统，以期实现英夫利昔单抗的高效包载，提高药物在肠道中的稳定性，延长药物在肠道内的滞留时间，促进药物在肠道炎症部位的靶向定位释放，最终达到口服英夫利昔单抗治疗炎症性肠病，降低其不良反应的目的。

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. It has a long treatment cycle, limited treatment, obvious side effects, high recurrence rate and many other issues, leading to a great impact on the patient's psychology, work and life. Infliximab, a anti-TNF monoclonal antibody, has been approved by CFDA for the treatment of IBD. However, obvious side effects was caused by intravenous administration of infliximab due to its non-targeting ability. To solve this problem, actually and theoretically we attemp to design a kind of infliximab incorporated nanocomplex for oral in the treatment of IBD. This nanocomplex will be prepared by phenylo boric acid modified hyaluronic acid polymers based on a protein-templated polymer self-assembly strategy. The resulted ROS-responsive nanocomplex may enhance the drug loading, improve the drug stability, prolong the residence time in the intestine, promote the drug release in the target site of IBD, and ultimately reduce the side effects of infliximab.