针对急性胰腺炎（AP）的靶向给药系统研究极为匮乏。首先胰腺腺泡细胞（PAC）紧密连接即血胰屏障影响了药物的治疗效果，其次PAC损伤是AP的始发因素，因此PAC靶向给药系统的开发对于AP的治疗具有重要的意义和应用前景。然而，如何实现高效精准靶向PAC是个亟待解决的问题。我们在前期研究中，以胰腺靶向前药的方法可明显减缓AP的病理进程，但也发现该给药系统靶向效率不足的缺陷。本课题利用PAC的生理特征及AP期间该细胞内微环境酶的差异，以谷氨酸、PEG及环糊精作为多重靶向定位的载体材料，设计一个先靶向胰腺病灶部位、可高效地被PAC摄取及利用损伤PAC细胞内微环境α-淀粉酶的差异实现药物快速释放的PAC靶向纳米给药系统。建立细胞和动物模型，以大黄酸为模型药物，研究该纳米粒对PAC的靶向定位能力。阐明其逐级靶向过程和抗炎机制，为探索新型给药系统治疗AP提供理论基础和实验依据。

Acute pancreatitis(AP) therapy is hindered by lack of targeting drug delivery system. Identifying and discovering a pancreatic acinar cell (PAC) targeted nanoparticle system which has ability to penetrate the tight junction of PAC (Blood-Pancreas-Barrier, BPB), has an important significance and broad application prospect. However, it is challenge to develop a drug delivery system to target PAC efficiently. In our previous study, pancreas targeted prodrug was used to treat AP, resulting in inhibition of pancreatic injury and suppressing the pathological process. However, the targeted efficiency to pancreas was not high. Based on the properties and intracellular microenvironment of PAC, in the present study, a multifunctional nanoparticle system for PAC was developed using β-cyclodextrin, PEG and glutamic acid. The nanoparticle system not only target to lesion area and PAC, but also release drugs quickly in PAC. Afterward, the targetability to injured tissue , targeted efficiency to PAC, and the drug release controllability would be studied using Rhein as the model drug. Moreover, the mechanistic study of the nanoparticle system would be performed. Therefore, this project is novel, and will be a beneficial trail for developing PAC targeted delivery system.