单克隆抗体的度依赖扩散:异常扩散的潜在机制
Gaurav Kumar1, Arezoo M Ardekani1
1School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Molecular pharmaceutics
|April 4, 2024
概括
抗体度高导致聚合和异常扩散由于自我关联. 分散粒子动力学揭示了库伦的吸引力驱动集中的单克隆抗体溶液中的聚合物形成.
科学领域:
- 生物物理学的生物物理.
- 材料科学 材料科学 材料科学
- 计算化学的计算化学
背景情况:
- 由于粘度和扩散限制,单克隆抗体 (mAbs) 的高度在开发,储存和传递方面存在挑战.
- 抗体自我结合和聚合是导致这些配方问题的关键因素.
研究的目的:
- 通过粗粒度模型,研究IgG1抗体分子在缩水溶液中的扩散行为.
- 了解在高抗体度下异常扩散和聚合形成背后的机制.
主要方法:
- 利用基于散射粒子动力学 (DPD) 的粗粒度模型来模拟抗体溶液.
- 通过将计算的结构因子与文献数据相匹配来确定粗粒度相互作用参数.
- 在各种NaCl和抗体度下分析了扩散系数 (D) 和异常扩散指数 (α).
主要成果:
- 观察到低抗体度 (10-25毫克/毫升) 的Fickian扩散,高度 (>50毫克/毫升) 的异常扩散.
- 在所有度中,异常扩散在大约0.330.4μs后过渡到Fickian扩散.
- 在扩散行为,总量和库伦相互作用能量之间发现了强烈的相关性.
结论:
- 静电互补区域之间的库伦引力驱动拥挤的抗体溶液中的聚合物形成.
- 这种静电相互作用是观察到异常扩散和随后的聚合的主要机制.
- 了解这些相互作用对于设计稳定,高度抗体配方至关重要.
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