Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Nanobiotechnology. 2020 Sep 15;18(1):133. doi: 10.1186/s12951-020-00693-4.
Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration.
All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17).
We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.
英夫利昔单抗（IFX），一种 TNF-α 阻断嵌合单克隆抗体，可诱导炎症性肠病（IBD）患者的临床反应和黏膜愈合。然而，该药物的全身给药会引起不良反应。与静脉给药相比，口服抗体治疗可能是治疗 IBD 的有效策略。
所有三种载体都具有高包封效率、窄粒径分布和最小的全身暴露。与 IBD 患者 PBMC 中的淋巴细胞相比，纳米复合载体与单核细胞之间的相互作用更高。靶向炎症性结肠炎的口服纳米复合载体给药可最大限度地减少全身暴露。与 DSS 治疗组相比，所有使用纳米复合载体的 IFX 给药制剂均显著减轻了结肠炎诱导的体重减轻、结肠缩短和组织形态学评分。与 DSS 治疗组相比，AC-IFX-L 和 EAC-IFX-L 组的疾病活动指数明显改善。此外，AC-IFX-L 和 EAC-IFX-L 减轻了促炎细胞因子的表达（Tnfa、Il1b 和 Il17）。
我们提出了口服抗体给药系统，该系统在改善小鼠结肠炎疗效的同时降低了全身暴露。这些口服给药系统为治疗 IBD 提供了一种有前途的治疗方法。
