目的：本研究旨在验证强啡肽A(1-8) [DYN-A(1-8)]纳米颗粒对脑缺血再灌注损伤大鼠的脑靶向性 和外周毒性。方法：使用聚柠檬酸酯-g-精氨酸（PCGA）为DYN-A(1-8)的药物运输载体制备DYN-PCGA 纳米颗粒，评测DYN-PCGA纳米颗粒表征。将荧光素Cy5标记的DYN-A(1-8)或 DYN-PCGA通过尾静脉 注射入大脑中动脉闭塞（MCAO）大鼠，应用小动物活体成像系统验证 DYN-PCGA的脑靶向能力。通过 HE染色观察DYN-A(1-8)纳米颗粒对MCAO大鼠心、肝、脾、肺、肾组织病理学的影响，评估尾静脉注射 DYN-PCGA的在体毒性。结果：纳米颗粒表征评测结果显示，DYN-PCGA(1∶5)具有粒径小、稳定性高、负 载能力强的特性。活体成像结果显示，DYN-PCGA在给药后能够有效地通过血脑屏障转运药物至大脑， 具有良好的脑靶向性。HE染色结果显示，MCAO大鼠的心、肝、脾、肺、肾的组织病理切片显示各组织细 胞结构正常，未见水肿和炎性细胞浸润，均未发现异常的组织病理学改变。结论：DYN-PCGA纳米颗粒延 长了DYN-A(1-8)的血浆半衰期，具有良好的脑靶向性和一定的安全性。

This study aimed to verify the brain targeting and peripheral toxicity of Deltorphin A(1-8) [DYN-A(1-8)] nanoparticles in rats with cerebral ischemia-reperfusion injury. Methods: DYN-A(1-8) was encapsulated into poly (citric acid)-g-arginine (PCGA) based nanoparticles, and the characteristics of DYN-PCGA nanoparticles were evaluated. Fluorescent Cy5-labeled DYN-A(1-8) or DYN-PCGA was injected into middle cerebral artery occlusion (MCAO) rats via the tail vein, and an in vivo imaging system was used to validate the brain targeting ability of DYN-PCGA. The effects of DYN-A(1-8) nanoparticles on the histopathology of heart, liver, spleen, lung, and kidney tissues in MCAO rats were observed by HE staining to assess the in vivo toxicity of DYN-PCGA administered via the tail vein. Results: The characterization results showed that DYN-PCGA(1∶5) exhibited small particle size, high stability, and strong drug loading capacity. In vivo imaging results indicated that DYN-PCGA could effectively transport drugs across the blood-brain barrier to the brain after administration, demonstrating good brain targeting. HE staining results revealed that the tissue sections of heart, liver, spleen, lung, and kidney in MCAO rats showed normal cellular structure without edema or inflammatory cell infiltration, and no abnormal histopathological changes were found. Conclusion: DYN-PCGA nanoparticles extended the plasma half-life of DYN-A(1-8), exhibiting good brain targeting and certain safety.