Ma Z, Qian P, Shen R, Hu B, He X, Gao F, Shen B, Zhang N, Shan Y, Shen X, Gao T, Jin L
Department of Department of Pathology and Molecular Medicine Center, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, ZJ, P.R.China.
Department of Department of Pathology and Molecular Medicine Center, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, ZJ, P.R.China.
Transplant Proc. 2019 Apr;51(3):960-965. doi: 10.1016/j.transproceed.2019.01.031. Epub 2019 Jan 9.
Hepatic ischemia/reperfusion-induced pancreatic injury (HI/RPI) is an important pathophysiological phenomenon in clinics. Exenatide is found to have hepatopancreatic protection; however, the half-life of exenatide is extremely short, which limits its clinical application. In the present study, we described an exenatide nanocarrier based on poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) and aimed to investigate the protective effects of exenatide/PLL-PEG-PLL on HI/RPI.
PLL-PEG-PLL was synthesized and estimated by being applied as a nanocarrier for lengthening delivery of exenatide. Exenatide was loaded into PLL-PEG-PLL by electrostatic interactions at pH 7.4. The loading and release of exenatide from PLL-PEG-PLL were characterized in vitro. The pancreatic protection of exenatide/PLL-PEG-PLL was assessed using the animal model, histopathological examination, blood biochemical indices detection, antioxidant activity, and anti-inflammatory evaluation in vivo.
Exenatide/PLL-PEG-PLL displayed efficient loading and sustained release. Exenatide/PLL-PEG-PLL complex moderated HI/RPI and enlarged islet functionality compared to free exenatide.
We propose that the nanocarrier PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting anti-HI/RPI pharmacotherapy with unprecedented clinical benefits.
肝缺血/再灌注诱导的胰腺损伤（HI/RPI）是临床上一种重要的病理生理现象。已发现艾塞那肽具有肝胰腺保护作用；然而，艾塞那肽的半衰期极短，这限制了其临床应用。在本研究中，我们描述了一种基于聚（L-赖氨酸）-聚（乙二醇）-聚（L-赖氨酸）（PLL-PEG-PLL）的艾塞那肽纳米载体，并旨在研究艾塞那肽/PLL-PEG-PLL对HI/RPI的保护作用。
合成PLL-PEG-PLL，并将其作为延长艾塞那肽递送的纳米载体进行评估。在pH 7.4条件下，通过静电相互作用将艾塞那肽负载到PLL-PEG-PLL中。在体外对艾塞那肽从PLL-PEG-PLL中的负载和释放进行表征。使用动物模型、组织病理学检查、血液生化指标检测、抗氧化活性和体内抗炎评估来评估艾塞那肽/PLL-PEG-PLL的胰腺保护作用。
艾塞那肽/PLL-PEG-PLL表现出高效负载和持续释放。与游离艾塞那肽相比，艾塞那肽/PLL-PEG-PLL复合物减轻了HI/RPI并增强了胰岛功能。
我们提出纳米载体PLL-PEG-PLL可能作为一种有效的艾塞那肽纳米载体，用于增强抗HI/RPI药物治疗，具有前所未有的临床益处。
