基化胰岛素装载的复合水凝用于受保护的口服输送
Melissa Kanzelberger Coolich1, Olivia L Lanier2, Ethan Cisneros3
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
概括
这项研究引入了用于口服蛋白质输送的新型聚甲基烯酸移植乙烯基醇凝. 这些凝保护像胰岛素这样的蛋白质免受降解,并通过粘膜粘合和PEGylation增强肠道吸收.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 蛋白质化学 蛋白质化学
背景情况:
- 现有的口服蛋白质输送系统努力保护蛋白质免受蛋白质分解的破坏.
- 对于pH敏感的载体往往缺乏足够的粘膜粘合,无法有效地通过肠道释放.
- 聚乙烯甘醇 (PEG) 链具有粘膜粘合和药物保护的潜力.
研究的目的:
- 开发和评估pH敏感的聚甲烯酸移植乙烯基醇 (PMAA-g-EG) 凝作为口服蛋白质输送的载体.
- 为了提高蛋白质的稳定性和肠道吸收,使用胰岛素的PEGylation.
- 研究PEG移植密度在载体加载和释放机制中的作用.
主要方法:
- 合成和P(MAA-g-EG) 凝的表征.
- 将PEG与胰岛素 (LysB29) 结合在一起,产生PEG化胰岛素 (PI).
- 使用Caco-2/HT-29-MTX共同培养的体外研究来评估细胞运输和体抵抗.
- 在Sprague-Dawley大鼠体内研究以测量胰岛素吸收和生物可用性.
主要成果:
- 甲-g-EG) 凝与基化胰岛素表现出pH敏感的H键相互作用,促进受控释放.
- 胰岛素的PEGylation改善了它对蛋白质分解的稳定性,并增强了粘膜粘合.
- 在体外和体外的研究证实了通过P(MAA-g-EG系统输送的PEGylated胰岛素的改善细胞运输和生物可用性.
- PEG移植密度影响了载体的加载和释放动力学.
结论:
- (MAA-g-EG) 凝代表了口服蛋白质输送的有希望的平台,提供了增强的保护和吸收.
- 胰岛素的PEGylation是一种有效的策略,可以改善其稳定性和粘膜粘合性,用于口服.
- 这种新的系统有可能改善基于蛋白质的治疗方法的治疗结果,例如糖尿病管理.
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