Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903, USA.
Pharm Res. 2012 Jun;29(6):1689-97. doi: 10.1007/s11095-012-0696-6. Epub 2012 Feb 14.
To investigate interactions between protein and silicone oil so that we can provide some mechanistic understanding of protein aggregation in silicone oil lubricated syringes and its prevention by formulation additives such as Polysorbate 80 and Poloxamer 188.
Interfacial tension values of silicone oil/water interface of abatacept solutions with and without formulation additives were obtained under equilibrium conditions using Attension Theta optical tensiometer. Their adsorption and desorption profiles were measured using Quartz Crystal Microbalancing with Dissipation monitoring (QCM-D). The degree of aggregation of abatacept was assessed based on size exclusion measurement.
Adsorption of abatacept at the oil/water interface was shown. Polysorbat 80 was more effective than Poloxamer 188 in preventing abatacept adsorption. Moreover, it was noted that some of the adsorbed abatacept molecules were not desorbed readily upon buffer rinse. Finally, no homogeneous aggregation was observed at room temperature and a slight increase of aggregation was only observed for samples measured at 40°C which can be prevented using Polysorbate 80.
Interfacial adsorption of proteins is the key step and maybe responsible for the phenomenon of soluble-protein loss when contacting silicone oil and the irreversible adsorption of protein may be associated with protein denaturation/aggregation.
研究蛋白质与硅油之间的相互作用，以便为硅油润滑注射器中蛋白质聚集及其通过配方添加剂（如聚山梨酯 80 和泊洛沙姆 188）的预防提供一些机制理解。
在平衡条件下，使用 Attension Theta 光学张力计获得含有和不含有配方添加剂的abatacept 溶液的硅油/水界面的界面张力值。使用石英晶体微天平（QCM-D）测量其吸附和脱附曲线。根据尺寸排除测量评估 abatacept 的聚集程度。
显示了 abatacept 在油/水界面的吸附。聚山梨酯 80 比泊洛沙姆 188 更有效地防止 abatacept 吸附。此外，注意到一些吸附的 abatacept 分子在缓冲液冲洗时不易脱附。最后，在室温下未观察到均相聚集，仅在 40°C 测量的样品中观察到轻微的聚集增加，这可以通过使用聚山梨酯 80 来预防。
蛋白质的界面吸附是关键步骤，可能是接触硅油时可溶性蛋白质损失的现象的原因，而蛋白质的不可逆吸附可能与蛋白质变性/聚集有关。
