用乌尔索西可酸装饰的Zwitterionic纳米颗粒用于口服肝脏向的密闭循环胰岛素输送
Yuhong Ma1, Wei Wang1, Caihua Li1
1Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Advanced healthcare materials
|January 21, 2024
概括
用ursodeoxycholic acid (UDCA) 装饰的新型zwitterionic纳米颗粒克服了肠道障碍,有效地提供口服胰岛素. 这一突破使得糖尿病小鼠每天一次的闭环血糖控制成为可能,显示出糖尿病治疗的前景.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 药理学 药理学是指药理学的学科.
背景情况:
- 口服胰岛素的输送面临着由于跨表皮屏障和降解的挑战.
- 现有的疗法在向肝脏和血糖反应方面扎.
- 开发有效的口服胰岛素配方对于糖尿病管理至关重要.
研究的目的:
- 设计装饰着ursodeoxycholic acid (UDCA) 的zwitterionic纳米颗粒,用于增强口服胰岛素的输送.
- 克服肠道障碍并准肝脏以改善胰岛素的生物可用性.
- 为了实现每天一次的口服胰岛素治疗与闭环血糖控制.
主要方法:
- 合成了装饰着UDCA的Zwitterionic纳米颗粒 (碳氧贝他因,CB) (UC-CMs@ins).
- 评估了粘液透性,细胞内化 (通过PAT1和ASBT) 和内分泌体逃逸.
- 基底侧胰岛素释放的评估是使用大胆胆胆酸结合蛋白和OSTα-OSTβ通路进行的.
- 在糖尿病小鼠的体内研究评估了血糖调节和食后葡萄糖水平.
主要成果:
- UC-CMs@ins显示出出色的粘液透性和增强的细胞吸收.
- 这些纳米颗粒表现出优异的内溶体逃逸和改善胰岛素释放.
- UDCA装饰促进了肝脏的积累,并防止了胰岛素的降解.
- 在糖尿病小鼠中,口服UC-CMs@ins可实现持续的正常血糖 (≈22小时).
结论:
- 与UDCA功能化的Zwitterionic纳米粒子有效地克服了口服胰岛素输送的肠道障碍.
- 开发的纳米粒子为每天一次的口服胰岛素治疗提供了一个有前途的平台.
- 这种方法显示出在糖尿病治疗中改善血糖控制的巨大潜力.
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