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具有ROS响应刚度调整的双屏障穿越脂质体,用于口服缺血性中风治疗

Jinjie Zhang¹, Jieke Zhang¹, Shuo Zhang²

¹School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, China.

Journal of controlled release : official journal of the Controlled Release Society

|June 17, 2025

概括

新的脂质体通过向营养物质运输体并响应氧化应激,通过口服提供中风药物. 这一突破增强了大脑的药物输送,改善了缺血性中风患者的治疗结果.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
神经科学是一个神经科学.

背景情况:

口服药物用于缺血性中风是理想的,但受到肠上皮层 (IEB) 和血脑屏障 (BBB) 的阻碍.
传统的纳米载体往往无法有效地穿越这些生物障碍.
开发有效的口服纳米载体用于针对大脑的治疗仍然是一个重大挑战.

研究的目的:

设计新型的双功能脂质体,以增强口服布甲酸 (NBP) 的输送,用于治疗缺血性中风.
用一个统一的纳米平台来克服IEB和BB,利用核酸转运器和ROS响应调制.
建立一种新的策略,用于"屏障适应性脂质体"用于口服脑部输送.

主要方法:

脂质体的功能化与两性性细胞胺-脂酸合物 (LA-C) 形成C-NBP.
利用cytidine对核酸转运体 (CNT1和ENT1) 的亲和力,用于肠道和BBB转位.
利用LA-C的滴醇环用于ROS响应膜调节和药物释放.

主要成果:

在老鼠中,C-NBP Lip获得了44.61%的口服生物利用率,与自由NBP (18.80%) 相比,增加了137%.
在短时间和长时间的老鼠缺血性中风模型中显示出显著的神经保护作用.
没有表现出可观察到的毒性,表明了有利的安全性.

结论:

工程设计的"障碍适应性脂质体"成功地整合了内源性输送器向和刺激反应药物释放.
这种纳米平台为口服大脑输送提供了一个变革性的方法,克服了关键的生物障碍.
开发的脂质体有望在缺血性中风干预中改善治疗策略.

关键词:

血液-大脑屏障是什么?赛蒂丁 (cytidine) 是一种类药物.缺血性中风是因为缺血性中风.脂质体是一种脂质体.通过口服进行管理.刚性调制的刚性调制方法

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