用不同的质谱技术对脂质体中的胰岛素和胆酸复合体进行表征
Dandan Sha1, Minghui Yuan1, Lin Zhang2
1Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, China.
Analytical and bioanalytical chemistry
|January 27, 2025
概括
胆酸,如陶罗胆酸 (TCA) 和糖胆酸 (GCA),与胰岛素非共价结合,增强口服生物可用性. 质谱学显示,TCA与胰岛素的结合力比GCA更强.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 制药科学 制药科学
背景情况:
- 口服胰岛素的输送面临着低生物可用性的挑战.
- 胆汁酸是改善胰岛素稳定性和吸收的潜在配体.
- 了解胰岛素 - 胆酸相互作用对于开发有效的口服胰岛素配方至关重要.
研究的目的:
- 描述胰岛素和胆酸 (TCA和GCA) 之间的非共价相互作用.
- 为了确定胰岛素 - 胆酸复合物的结合亲和和度和固基度.
- 探索口服配方中的胆酸对胰岛素保护的机制.
主要方法:
- 电子喷射电离质谱 (ESI-MS) 和合MS (MS/MS) 用于复杂的识别和亲和度的确定.
- 离子移动性质谱仪 (IMMS) 用于分离和分析复杂的混合物.
- 通过ESI-MS进行脂质体的准备和表征.
- 分子对接模拟 (AutoDock) 用于预测结合点和机制.
主要成果:
- 通过非共价键,ESI-MS证实了胰岛素-GCA和胰岛素-TCA复合物的形成.
- 与GCA相比,TCA对胰岛素的结合亲和力更强,这是MS/MS数据和关联常数所支持的.
- IMMS成功地分离了各种胰岛素胆酸复合物,揭示了不同的趋势.
- 在脂质体配方中检测到胰岛素 - 胆酸相互作用产物,表明成功封装和相互作用.
结论:
- 陶罗胆酸和糖胆酸可以与胰岛素形成稳定的非共价复合体.
- 与GCA相比,TCA对胰岛素的结合亲和力更高.
- 这些发现为口服输送系统中胰岛素胆酸的保护机制提供了洞察力.
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