|
| 强啡肽A(1-8)纳米颗粒的脑靶向性和外周毒性的研究 |
| Study on brain targeting and toxicity of dynorphin A(1-8) nanoparticles |
| 投稿时间：2024-11-29 修订日期：2024-11-29 |
| DOI： |
| 中文关键词: 强啡肽A(1-8) 纳米颗粒 脑靶向性 毒性 |
| 英文关键词: dynorphin A(1-8) nanoparticles brain targeting toxicity |
| 基金项目: |
|
| 摘要点击次数: 117 |
| 全文下载次数: 0 |
| 中文摘要: |
| 目的：本研究旨在验证强啡肽A(1-8) [dynorphin 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（polycitrate-g-arginine，PCGA）为DYN-A(1-8) 的药物运输载体制备DYN-PCGA纳米颗粒。应用小动物活体成像系统验证 DYN-PCGA的脑靶向能力。通过对大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）大鼠的心、肝、脾、肺、肾组织学观察评估尾静脉DYN-PCGA的在体毒性。结果：静脉DYN组从给药后一直未见明显的脑内荧光信号；而静脉DYN-PCGA组从给药后25 min开始出现脑内荧光信号，并持续到50 min左右荧光信号消失。经尾静脉给予有效剂量DYN-PCGA 后，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，且在给药后能够有效地通过BBB转运药物至大脑，具有良好的脑靶向性。DYN-PCGA 纳米颗粒对大鼠的心、肝、脾、肺、肾等主要脏器无毒性作用，具有一定的安全性。 |
| 英文摘要: |
| OBJECTIVE To investigate the brain targeting and toxicity of DYN-A(1-8) nanoparticles on cerebral ischemia-reperfusion in rats. METHODS The DYN-A(1-8)-loaded polycitrate-g-arginin (PCGA) nanoparticles (DYN-PCGA) were prepared and characterized. The brain targeting ability of DYN-PCGA was verified by small animal imaging system. Study on middle cerebral artery occlusion (MCAO) rats' heart, liver, spleen, lung and kidney to evaluate the toxicity of DYN-PCGA. RESULTS There was no obvious fluorescence signal in the brain after intravenous DYN administration; while the intracerebral fluorescence signal appeared from 25 min to 50 min after intravenous DYN-PCGA administration. The histopathological sections of the heart, liver, spleen, lung and kidney of MCAO rats showed normal cell structure, no edema and inflammatory cell infiltration, and no abnormal histopathological changes were found. CONCLUSION DYN-PCGA nanoparticles can prolong the plasma half-life of DYN-A(1-8), and can effectively transport drugs to the brain via BBB with good brain targeting. DYN-PCGA nanoparticles have certain safety, and showing no toxic effect on the heart, liver, spleen, lung and kidney of rats. |
|
View Fulltext
查看/发表评论 下载PDF阅读器 |
| 关闭 |