具有仿生表面的纳米复合乳负载艳山姜挥发油用于防治糖尿病血管内皮损伤的研究

血管内皮损伤是糖尿病心血管并发症发展与恶化的始动因素与关键环节，因而开发高效的药物及其制剂用于防治糖尿病血管内皮损伤成为了研究焦点。本课题组前期研究发现，民族药提取物--艳山姜挥发油（EOFAZ）对糖尿病引起的血管内皮损伤具有良好的防治效果，其机制与改善氧化应激和抑制炎症反应有关。然而，EOFAZ水溶性差、口服生物利用度低，亟需开发新型口服制剂用于临床治疗。本项目设计并构建了一种具有仿生表面的多糖-蛋白纳米复合乳，力求提高EOFAZ水溶性和稳定性，延长胃肠道滞留时间，协助其克服胃肠屏障。其中，核心技术问题是模仿病毒通过蛋白糖基化作用入侵黏膜组织的行为特点，协调乳剂中关键表面组分--“葡聚糖”和“鱼精蛋白”的细微平衡，促进制剂跨粘液层和小肠上皮细胞转运，提高EOFAZ的口服生物利用度，增强其体内药效。本研究将围绕EOFAZ的纳米递送平台开发进行系统的研究，为糖尿病内皮损伤的防治提供新思路。

Vascular endothelial injury is a key point and initiating factor in the development and deterioration of diabetic cardiovascular complications. Therefore, the development of effective drugs and their preparations for the prevention and treatment of vascular endothelial injury induced by diabetes has become the focus of research. In the previous studies, our research group found that the essential oil of Alpinia zerumbet (EOFAZ) has a good preventive and therapeutic effect on endothelial injury induced by diabetes, and its mechanism is related to the amelioration of oxidative stress and inhibition of inflammatory reactions. However, new oral formulations of EOFAZ is highly in need due to its poor water solubility and low oral bioavailability. In this project, a polysaccharide-protein nanocomposite emulsion with bionic surface was designed and constructed for the delivery of EOFAZ via improving its water solubility and stability, prolonging the retention time in gastrointestinal tract and overcoming the gastrointestinal barriers. In the development of EOFAZ nanocomposite emulsion, the core technical issue is to imitate the behavioral characteristics of viruses invading mucosal tissues through protein glycosylation. Therefore, the coordination on the fine balance between the key surface components in the emulsion-"dextran" and "protamine" might promote the transport across mucus layer and small intestinal epithelial cells, resulting in improved oral bioavailability, which enhances the efficacy of EOFAZ in vivo. This study will focus on the development of a nanoplatform for the delivery of EOFAZ to provide a new way of thinking for the prevention and treatment of endothelial injury induced by diabetes.