Influence of Protein Adsorption on Aggregation in Prefilled Syringes
Influence of Protein Adsorption on Aggregation in Prefilled Syringes
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预充式注射器中蛋白质吸附对聚集的影响
DOI：
10.1016/j.xphs.2021.07.007
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发表时间：
2021
影响因子：
3.8
通讯作者：
Uchiyama Susumu
中科院分区：
文献类型：
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作者：
Yoneda Saki;Maruno Takahiro;Mori Asuka;Hioki Ayana;Nishiumi Haruka;Okada Rio;Murakami Makoto;Zekun Wang;Fukuhara Ayano;Itagaki Nozomi;Harauchi Yosuke;Adachi Satoru;Okuyama Kumi;Sawaguchi Taichi;Torisu Tetsuo;Uchiyama Susumu
预充式注射器（PFS）中蛋白质聚集体的形成可受到固液界面处蛋白质吸附和解吸的影响。虽然抑制PFS表面上的蛋白质吸附可导致聚集量减少，但PFS中蛋白质吸附介导的聚集的潜在机制尚不清楚。本研究考察了蛋白质吸附在不含硅油的PFS表面[硼硅酸盐玻璃（GLS）和环烯烃聚合物（COP）]上引起的蛋白质聚集以及影响PFS表面蛋白质吸附的因素。吸附的蛋白质形成多层结构，由两种不同类型的层组成：吸附在材料表面的蛋白质和吸附在表面蛋白质顶部的蛋白质。蛋白质吸附在GLS表面的主要动力是pH值依赖的静电相互作用，而蛋白质吸附在COP表面的疏水作用占主导地位。当蛋白质之间的排斥力较弱时，两种材料在吸附蛋白质层上的蛋白质吸附增加，结果，蛋白质聚集增加。因此，具有高胶体稳定性的制剂可以使COP表面上的蛋白质吸附最小化，导致蛋白质聚集减少。
Protein aggregate formation in prefilled syringes (PFSs) can be influenced by protein adsorption and desorption at the solid–liquid interface. Although inhibition of protein adsorption on the PFS surface can lead to a decrease in the amount of aggregation, the mechanism underlying protein adsorption-mediated aggregation in PFSs is unclear. This study investigated protein aggregation caused by protein adsorption on silicone oil-free PFS surfaces [borosilicate glass (GLS) and cycloolefin polymer (COP)] and the factors affecting the protein adsorption on the PFS surfaces. The adsorbed proteins formed multilayered structures that consisted of two distinct types of layers: proteins adsorbed on the surface of the material and proteins adsorbed on top of the proteins on the surface. A pH-dependent electrostatic interaction was the dominant force for protein adsorption on the GLS surface, while hydrophobic effects were dominant for protein adsorption on the COP surface. When the repulsion force between proteins was weak, protein adsorption on the adsorbed protein layer was increased for both materials and as a result, protein aggregation increased. Therefore, a formulation with high colloidal stability can minimize protein adsorption on the COP surface, leading to reduced protein aggregation.