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聚二甲基硅氧烷/水界面上单克隆抗体和非离子表面活性剂的竞争吸附。

Competitive Adsorption of a Monoclonal Antibody and Nonionic Surfactant at the PDMS/Water Interface.

机构信息

Biological Physics Laboratory, Department of Physics and Astronomy, University of Manchester, Oxford Road, Schuster Building, Manchester M13 9PL, U.K.

National Graphene Institute, University of Manchester, Oxford Road, Schuster Building, Manchester M13 9PL, U.K.

出版信息

Mol Pharm. 2023 May 1;20(5):2502-2512. doi: 10.1021/acs.molpharmaceut.2c01099. Epub 2023 Apr 3.

Abstract

Interfacial adsorption of monoclonal antibodies (mAbs) can cause structural deformation and induce undesired aggregation and precipitation. Nonionic surfactants are often added to reduce interfacial adsorption of mAbs which may occur during manufacturing, storage, and/or administration. As mAbs are commonly manufactured into ready-to-use syringes coated with silicone oil to improve lubrication, it is important to understand how an mAb, nonionic surfactant, and silicone oil interact at the oil/water interface. In this work, we have coated a polydimethylsiloxane (PDMS) nanofilm onto an optically flat silicon substrate to facilitate the measurements of adsorption of a model mAb, COE-3, and a commercial nonionic surfactant, polysorbate 80 (PS-80), at the siliconized PDMS/water interface using spectroscopic ellipsometry and neutron reflection. Compared to the uncoated SiO surface (mimicking glass), COE-3 adsorption to the PDMS surface was substantially reduced, and the adsorbed layer was characterized by the dense but thin inner layer of 16 Å and an outer diffuse layer of 20 Å, indicating structural deformation. When PS-80 was exposed to the pre-adsorbed COE-3 surface, it removed 60 wt % of COE-3 and formed a co-adsorbed layer with a similar total thickness of 36 Å. When PS-80 was injected first or as a mixture with COE-3, it completely prevented COE-3 adsorption. These findings reveal the hydrophobic nature of the PDMS surface and confirm the inhibitory role of the nonionic surfactant in preventing COE-3 adsorption at the PDMS/water interface.

摘要

单克隆抗体 (mAb) 的界面吸附会导致结构变形,并引起不需要的聚集和沉淀。非离子表面活性剂通常被添加到制造、储存和/或给药过程中,以减少 mAb 的界面吸附。由于 mAb 通常被制成涂有硅油的即用型注射器,以改善润滑性,因此了解 mAb、非离子表面活性剂和硅油在油/水界面的相互作用非常重要。在这项工作中,我们在光学平整的硅衬底上涂覆了聚二甲基硅氧烷 (PDMS) 纳米膜,以便使用光谱椭圆术和中子反射法测量模型 mAb COE-3 和商业非离子表面活性剂聚山梨醇酯 80 (PS-80) 在硅化 PDMS/水界面的吸附。与未涂覆的 SiO 表面(模拟玻璃)相比,COE-3 吸附到 PDMS 表面的量大大减少,吸附层的特征是内层致密但较薄,厚度为 16 Å,外层扩散层为 20 Å,表明结构变形。当 PS-80 暴露于预先吸附的 COE-3 表面时,它去除了 60 wt %的 COE-3,并形成了一个具有相似总厚度 36 Å 的共吸附层。当 PS-80 首先注入或与 COE-3 混合时,它完全阻止了 COE-3 的吸附。这些发现揭示了 PDMS 表面的疏水性,并证实了非离子表面活性剂在防止 PDMS/水界面上 COE-3 吸附方面的抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/168a/10155179/303417d6936c/mp2c01099_0002.jpg

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