Engineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, Boston, MA, USA.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Mater. 2018 Sep;17(9):834-842. doi: 10.1038/s41563-018-0106-5. Epub 2018 Jun 11.
The gastrointestinal tract is the site of most drug delivery and therapeutic interventions for the management and treatment of numerous diseases. However, selective access to its mucosa, especially in the small bowel, is challenging. Here we develop an orally administered gut-coating formulation that provides a transient coating of the bowel. Through a materials screening campaign, we identified a sucrose octasulfate aluminium complex and further engineered the pH-dependent material into a complex coacervate formulation linked via pH-independent electrostatic interaction, which allowed an effective transient physical coating on the gastrointestinal mucosa, independent of gastric acid exposure. We tested the therapeutic values of this technology in two settings. Oral administration of this gut-coating formulation modulated the nutrient contact with bowel mucosa, which lowered the glucose responses in rodent models indicating a potential therapeutic utility in diabetes. Furthermore, the formulation protected biological agents from gastric acid exposure and degradation, which enabled oral delivery to the small bowel mucosa.
胃肠道是大多数药物输送和治疗干预的部位，可用于管理和治疗许多疾病。然而，选择性地进入其黏膜，特别是在小肠中，是具有挑战性的。在这里，我们开发了一种口服肠道涂层制剂，可提供肠道的短暂涂层。通过材料筛选活动，我们确定了八硫酸蔗糖铝络合物，并进一步将该 pH 依赖性材料设计成一种复杂凝聚物制剂，通过 pH 独立的静电相互作用连接，从而可以在不接触胃酸的情况下在胃肠道黏膜上形成有效的瞬时物理涂层。我们在两种情况下测试了该技术的治疗价值。口服这种肠道涂层制剂可以调节营养物质与肠道黏膜的接触，从而降低啮齿动物模型中的葡萄糖反应，表明其在糖尿病治疗方面具有潜在的应用价值。此外，该制剂可以保护生物制剂免受胃酸暴露和降解，从而能够将其递送到小肠黏膜。
