Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.
Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.
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通过原位口服负载抗体的水凝胶微胶囊来恢复结肠炎症的微生态
DOI：
10.1016/j.bioactmat.2021.12.022
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发表时间：
2022-09
影响因子：
18.9
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Li B;Li X;Chu X;Lou P;Yuan Y;Zhuge A;Zhu X;Shen Y;Pan J;Zhang L;Li L;Wu Z
与其他给药途径相比，治疗性抗体（如单克隆抗体）的原位口服给药用于慢性炎症治疗是最方便的方法。此外，肠道微生物群与结肠炎症之间的丰富联系表明肠道微生物群对结肠炎症的协同或拮抗作用。然而，由于不利的条件，抗体活性在通过胃肠道转移时会受到显著影响。此外，这些抗体具有短的血清半衰期，因此，需要以高剂量频繁施用才有效，导致患者耐受性低。本研究利用微流控技术制备水凝胶微囊作为口服给药载体。通过将抗体包封在这些微胶囊中，抗体在恶劣的胃肠道环境中存活，并通过口服给药途径快速释放到小肠中，达到与通过结肠炎症疾病模型评估的静脉注射相同的治疗效果。此外，作为炎症改善的指示的一些肠道微生物的丰度在原位载有抗体的微胶囊递送后显著改变，这意味着肠道微生态的恢复。这些发现证明我们的微囊被开发作为一种有效的口服递送剂的抗体在临床应用中具有可编程的功能。口服载抗体核壳微胶囊治疗结肠炎。核壳微囊在结肠腔中释放抗体，并减少易燃反应，从而重建肠道微生物群的平衡。这种薄壳水凝胶微胶囊使用油包水作为模板，通过微流体技术用于口服递送抗体，以保护免受不利的胃微环境的影响，并在小肠中快速释放而不失去其活性。壳层含有一个双重交联网络，这归因于其离子交联和共价交联功能。载抗体微囊在DSS诱导的结肠炎症疾病模型中显示出很好的治疗效果，其与静脉注射治疗的效果接近。口服携带抗体的微胶囊可恢复肠道微生态失调。采用微流控技术，以油包水为模板，制备了用于口服递送抗体的薄壳水凝胶微胶囊，以保护其免受不利的胃微环境的影响，并在小肠中快速释放而不丧失其活性。
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. Orally Administered Antibody-laden Core-shell Microcapsules for Colonic Inflammation. The core-shell microcapsules release antibodies in the colonic lumen, and reduce the inflammable reaction, thereby recreate the balance of intestinal microbiota. This thin shell hydrogel microcapsules using a water-in-water-in-oil as the template by microfluidic technique for orally delivery of antibodies is generated to protect from hostile stomach microenvironment and rapid released in the small intestine without losing their activity. The shell contains a double crosslinked network attributed to its ionic crosslinking and covalent crosslinking functionalities. The antibody-laden microcapsules demonstrate great therapeutic efficacy in DSS-induced colonic inflammation disease models, which is approximated to that of the intravenous injection treatment. Orally taken antibody-laden microcapsules restore the intestinal micro-ecological dysbiosis. The thin shell hydrogel microcapsules using a water-in-water-in-oil as the template by microfluidic technique for orally delivery of antibodies is generated to protect from hostile stomach microenvironment and rapid released in the small intestine without losing their activity.
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