在高度的mAb溶液中将表面活动与接口诱导的聚合相关联
Estephanie L N Escobar1, Valerie P Griffin1, Prajnaparamita Dhar1
1Department of Chemical and Petroleum Engineering, The University of Kansas, 1530W 15th Street, Lawrence, Kansas 66045, United States.
Molecular pharmaceutics
|February 22, 2024
概括
接口诱导的蛋白质聚合是高度抗体 (mAb) 疗法的一个问题. 表面活性剂的添加可能不会在高度下防止颗粒的形成,这凸显了表面活性剂与mAb比率的重要性.
科学领域:
- 生物制药制造业 生物制药制造业
- 蛋白质聚合科学 蛋白质聚合科学
- 制定 发展 制定 发展
背景情况:
- 界面诱导的聚合是制造和储存蛋白质治疗药物的关键问题,特别是在高度下.
- 了解蛋白质度和界面诱导的粒子形成之间的关系至关重要.
- 聚酸盐表面活性剂在高度下阻止蛋白质聚合的确切机制尚未完全理解.
研究的目的:
- 为了研究介面诱导的蛋白质颗粒形成对散装蛋白质度的依赖性.
- 阐明聚酸盐20 (PS20) 在缓解空气-水界面蛋白质聚合中的作用.
- 确定影响高度单克隆抗体 (mAb) 配方表面活性剂有效性的关键因素.
主要方法:
- 采用张力计技术,以不同度测量mAb的表面压力,使用或不使用PS20.
- 采用微流成像,将吸附动力学与空气-水界面和散装溶液中的可见蛋白质颗粒形成相关联.
- 分析了空气-水界面上的蛋白质和表面活性剂吸附行为.
主要成果:
- 在散装中的可见粒子形成与没有表面活性剂的mAb度线性增加.
- 界面粒子形成显示了对mAb度的对数依赖.
- 在低mAb度 (10 mg/mL) 时,PS20在CMC上方的添加减少了颗粒的形成.
- 在高mAb度 (170 mg/mL) 时,mAb和PS20的共同吸收发生,PS20无法防止颗粒形成.
结论:
- 表面活性剂与mAb分子的比率是防止高度mAb治疗中蛋白质颗粒形成的关键参数.
- 表面活性剂在缓解聚合的有效性取决于度,并受到共吸收现象的影响.
- 这些发现为优化高度蛋白质制药的配方提供了必要的见解.
相关概念视频
01:10Antibody Structure
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Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
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01:25Antibody Structure and Classes
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