基于基托桑的表面调制核心纳米颗粒,通过平衡粘液透和细胞吸收来口服输送exenatide
Yiyao Li1, Huixian Tian1, Han Zeng1
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 Liaoning, PR China.
International journal of pharmaceutics
|February 8, 2025
概括
通过使用新型核心纳米粒子,改善了口服和蛋白质药物输送. 这些酸盐涂层的纳米颗粒增强细胞吸收和通过肠道屏障的运输,为口服药物管理提供了一个有希望的策略.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术用于药物输送.
- 胃肠道药理学 胃肠道药理学
背景情况:
- 口服和蛋白质药物 (PDs) 由于肠道粘膜的透性而具有挑战性.
- 现有的纳米载体往往难以有效地克服粘液层和上皮壁垒.
- 粘液透与细胞吸收需要不同的表面特性.
研究的目的:
- 设计和开发具有平衡的粘液透和细胞吸收能力的新型纳米粒子 (NP).
- 通过使用这些工程NP来提高exenatide (EXT) 的内细胞分解效率和口服输送.
- 评估开发的纳米载体系统口服药物输送的体内疗效.
主要方法:
- 通过双重乳化和界面交叉连接,制造带有表达物 (EXT) 的卵子/德克斯/牛血清白蛋白 (EDB) NP,通过三甲酸 (STMP) 固化.
- 将EDB NP涂上阴离子多电解质奇托 (CS) ,以形成CS-EDB NP.
- 对CS-EDBNP (封装效率,颗粒大小,Zeta潜力) 的表征以及粘液透 (Transwell模型) 和细胞吸收/传输 (Caco-2/E-12共同培养模型) 的评估.
主要成果:
- CS-EDB NPs显示了高封装效率 (83.50 ± 0.44%),粒子大小 (~277 nm) 和泽塔电位 (-16.2 mV).
- CS-EDB NPs显示粘液透率降低 (1.1倍减少),但细胞吸收量显著增加 (2.15倍) 和通过能量依赖性内细胞和巨细胞通过能量依赖性内细胞和巨细胞转移 (1.77倍) 显著增加.
- 在体内研究显示了13.29%的药理生物可用性,有效的血糖和脂质调节,并在长期服用时改善了岛屿功能.
结论:
- 核心外结构的CS-EDBNP有效地保护胃肠道内的药物.
- 尽管粘液透有轻微的妥协,但NP实现了增强的内细胞和细胞吸收.
- 这种纳米载体系统为改善和蛋白质药物的口服输送提供了一个有希望的策略.
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