Li Bo, Li Xin, Chu Xiaodong, Lou Pengcheng, Yuan Yin, Zhuge Aoxiang, Zhu Xueling, Shen Yangfan, Pan Jinghua, Zhang Liyuan, Li Lanjuan, Wu Zhongwen
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Bioact Mater. 2021 Dec 25;15:305-315. doi: 10.1016/j.bioactmat.2021.12.022. eCollection 2022 Sep.
In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.
与其他给药途径相比,原位口服递送治疗性抗体(如单克隆抗体)用于慢性炎症治疗是最便捷的方法。此外,肠道微生物群与结肠炎症之间存在丰富的联系,这表明肠道微生物群对结肠炎症具有协同或拮抗作用。然而,由于恶劣的条件,抗体在通过胃肠道转运时活性会受到显著影响。此外,这些抗体的血清半衰期较短,因此需要频繁高剂量给药才能有效,导致患者耐受性较低。在此,我们开发了一种策略,利用微流控技术制备的薄壳水凝胶微胶囊作为口服递送载体。通过将抗体包裹在这些微胶囊中,抗体能够在恶劣的胃肠道环境中存活,并通过口服途径迅速释放到小肠中,通过结肠炎症疾病模型评估,其治疗效果与静脉注射相同。此外,原位递送载有抗体的微胶囊后,作为炎症改善指标的一些肠道微生物的丰度发生了显著变化,这意味着肠道微生态的恢复。这些发现证明我们的微胶囊可作为一种高效的口服递送剂,在临床应用中用于具有可编程功能的抗体。