糖尿病足部溃疡（糖足）是糖尿病的主要并发症之一，由高糖损伤血管内皮细胞造成糖尿病下肢动脉堵塞所致。血管生成样蛋白3（ANGPTL3）由肝分泌入血，调控血管内皮细胞附着和迁徙，促进血管生成，糖足局部治疗具有非常大的潜力，但缺乏相应的药物载体。已有研究报道，注射微泡、水凝胶等体系的载药体系可用于糖足的治疗，但是微纳米微泡注射到局部后易于流失；而水凝胶负载药物后药物释放速度往往过快，难以达到治疗效果。本研究结合微泡和水凝胶的优势，采用聚内酯微泡作为直接载体负载ANGPTL3，再通过水凝胶负载微泡后，注射到糖足成胶，保证持续释放有效浓度的ANGPTL3，达到促进血管生成的效果。同时由于聚内酯和水凝胶材料均可降解，体内无残留，具有安全性。本申请项目拟利用材料学及生物学对ANGPTL3在局部释放行为的控制及治疗效果进行评估，建立缓释体系-ANGPTL3释放-治疗效果之间的构效关系图谱。

Diabetic foot ulcer is one of the main complications and main cause of disability in patients with diabetes mellitus. Diabetic foot is the result of hyperglycemia-induced vascular endothelial cell injury and dysfunction which lead to artery occlusion. Angiogenesis like protein 3 is exclusively produced by hepatocytes. Upon secretion, it could bind vascular endothelial cells through integrin αvβ3 receptor and regulate cell adhesion and migration for angiogenesis. Topical administration of ANGPTL3 could be beneficial for endothelial cell protection and has great potential in the treatment of diabetic feet. However, there is a lack of suitable drug carriers for ANGPTL3. It has been reported that the drug delivery systems such as injecting microbubbles or hydrogels can be used for the treatment of diabetic feet. However, the micronano microbubbles are easy to drain after being injected into the local area and the drug release rate is often too fast after being loaded with hydrogel, both of which are the obstacles to achieve the therapeutic effect. Giving that hydrogel has great advantages in biocompatibility, hydrogel could serve as vehicle for ANGPTL3 application onto diabetic foot. By doing so, the sustained ANGPTL3 concentration could be obtained in foot ulcer to achieve desirable angiogenic effect. In the meantime, hydrogel materials are degraded along with the release of drug for safety. The aim of this project is to evaluate the regulation and therapeutic effect of ANGPTL3 in local release behavior and to establish a structure-effect relationship map between the release-treatment effect of the sustained release system and the effect of ANGPTL3.