炎症响应性自组装纳米药物对炎症性肠病的治疗研究

炎症性肠病是一种引起胃肠道炎症的慢性特发性疾病，目前尚无治愈的药物，开发新型的对炎症性肠病具有针对性的药物递送系统在炎症性肠病的临床治疗方面有着十分迫切的需求。纳米颗粒在结肠炎症位点有着被动靶向作用，因此适合作为药物递送载体应用于炎症性肠病的治疗。本项目拟通过利用天然多酚单宁酸、糖皮质激素地塞米松与多种响应性PEG高分子自组装构建炎症性肠病响应的纳米药物，其载体材料具有非常好的生物安全性，其纳米尺寸和负表面ζ电势有助于肠炎被动靶向，我们还设计了多种针对肠炎微环境响应可断裂结构，可筛选响应性最优化的纳米药物，降低激素暴露，减少副作用。并且该纳米药物具有较好活性氧清除能力，能够清除对肠道粘膜有破坏性的过量活性氧。该项目有望为炎症性肠病的治疗提供一种新型安全高效的纳米药物，并对其他难治性炎症的药物开发亦有启发作用。

Inflammatory bowel disease is a chronic gastrointestinal disease. Currently, there is no cure for the disease. Thus there is a very pressing need for the development of new drug delivery system targeting inflammatory bowel disease. The passive targeting role in the inflamed colon makes nanoparticles suitable as drug delivery carrier for the treatment of inflammatory bowel disease. This project intends to construct an inflammatory bowel disease responsive nano-drug through self-assembly of natural polyphenol tannic acid, glucocorticoid dexamethasone, and various responsive PEG polymers. The carrier has very good biosafety. Nano-size and negative surface zeta potential of nanocarier contribute to the passive targeting of the inflammatory colon. Furthermore, we designed a variety of microenvironment-responsive degradable structures for the inflammatory colon to screen for the optimized nano-drug, reducing corticosteroid exposure and reducing side effects. And the nano-drug has strong ability to scavenge reactive oxygen species and can remove excess reactive oxygen species that are damaging to the intestinal mucosa. The project is expected to provide a new type of safe and effective drug for the treatment of inflammatory bowel disease and also provide inspiration for the development of other refractory inflammatory drugs.