化学
单体
蛋白质聚集
精氨酸
动态光散射
单克隆抗体
静态光散射
色谱法
胶体
生物物理学
生物化学
氨基酸
聚合物
抗体
有机化学
纳米颗粒
化学工程
生物
工程类
免疫学
作者
Priscilla Kheddo,Malgorzata B. Tracka,Jonathan Armer,Rebecca J. Dearman,Shahid Uddin,Christopher F. van der Walle,Alexander P. Golovanov
标识
DOI:10.1016/j.ijpharm.2014.06.053
摘要
Finding excipients which mitigate protein self-association and aggregation is an important task during formulation. Here, the effect of an equimolar mixture of l-Arg and l-Glu (Arg·Glu) on colloidal and conformational stability of four monoclonal antibodies (mAb1-mAb4) at different pH is explored, with the temperatures of the on-set of aggregation (Tagg) and unfolding (Tm1) measured by static light scattering and intrinsic fluorescence, respectively. Arg·Glu increased the Tagg of all four mAbs in concentration-dependent manner, especially as pH increased to neutral. Arg·Glu also increased Tm1 of the least thermally stable mAb3, but without similar direct effect on the Tm1 of other mAbs. Raising pH itself from 5 to 7 increased Tm1 for all four mAbs. Selected mAb formulations were assessed under accelerated stability conditions for the monomer fraction remaining in solution after storage. The aggregation of mAb3 was suppressed to a greater extent by Arg·Glu than by Arg·HCl. Furthermore, Arg·Glu suppressed the aggregation of mAb1 at neutral pH such that the fraction monomer was near to that at the more typical formulation pH of 5.5. We conclude that Arg·Glu can suppress mAb aggregation with increasing temperature/pH and, importantly, under accelerated stability conditions at weakly acidic to neutral pH.
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