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具有 Propionate 功能的奇托桑水凝纳米颗粒,用于有效口服输送胰岛素

Yaqiong Chen¹, Hongdong Song², Xinyue Wang³

¹School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.

International journal of biological macromolecules

|December 26, 2024

概括

通过使用酸盐修饰的奇托桑纳米颗粒改善了口服胰岛素的输送. 这种新的方法提高了胰岛素的吸收和生物可用性,为糖尿病管理提供了注射的有希望的替代方案.

科学领域:

生物材料科学生物材料科学
药物运输药物运输药物运输
纳米技术纳米技术

背景情况:

像胰岛素这样的大分子药物的口服药物由于胃肠道环境而具有挑战性,导致生物可用性差.
素 (CS) 纳米粒子正在探索药物输送,但需要进行修改以提高有效性.
酸盐的酸盐修饰为改善药物运输提供了潜力.

研究的目的:

开发含有胰岛素的酸盐修饰的酸盐水凝纳米颗粒 (IN-CS/PA HNPs),用于增强口服输送.
研究纳米颗粒在胃肠道环境中的保护作用.
评估由单碳酸盐输送蛋白1 (MCT1) 介导的向和输送机制,并评估糖尿病大鼠的低血糖效应.

主要方法:

制造含有胰岛素的修改为酸的CS水凝纳米粒子 (IN-CS/PA HNPs).
封装效率和装载能力的确定.
使用Caco-2细胞的体外研究和使用大鼠结合肠环的体内研究来评估透性和吸收.
在1型糖尿病 (T1D) 的老鼠中评估低血糖效应和相对口服生物可用性.

主要成果:

在IN-CS/PA HNP中,胰岛素的封装效率高 (>95%) 和负载能力高 (~10%).
与未经修改的纳米颗粒相比,纳米颗粒在胃肠道中为胰岛素提供了更好的保护.
通过MCT1介导的内细胞分解显著提高了胰岛素的透性和在肠道上皮层的吸收.
在T1D大鼠中,口服IN-CS/PA HNP导致稳定,长期的低血糖效应,并显著改善了口服生物可用性 (2.29倍与空HNP相比,11.88倍与免费胰岛素相比).

结论:

酸功能化奇托桑水凝纳米颗粒通过克服胃肠道障碍,有效地改善口服胰岛素的吸收.
开发的纳米粒子提供了一个有前途的积极向策略,用于口服的宏分子药物.
这种方法代表了非侵入性糖尿病治疗的重大进步,可能减少对皮下胰岛素注射的依赖.

关键词:

基托桑是一种酸盐.水凝纳米颗粒的使用.胰岛素是一种胰岛素.针对MCT1进行定位.这是口头传递.

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