Spheryx, Inc., 330 East, 38th Street #48J, New York, New York 10016.
Spheryx, Inc., 330 East, 38th Street #48J, New York, New York 10016.
J Pharm Sci. 2019 Jan;108(1):155-161. doi: 10.1016/j.xphs.2018.10.002. Epub 2018 Oct 10.
Characterizing protein aggregates in the presence of silicone oil is a long standing challenge for the pharmaceutical industry. Silicone oil is often used as a lubricant in devices that deliver and store therapeutic protein products and has been linked to protein aggregation, which can compromise a drug's effectiveness or cause autoimmune responses in patients. Most traditional technologies cannot quantitatively distinguish protein aggregates and silicone oil in their native formulations for sizes less than 5 μm. We use holographic video microscopy to study protein aggregation to demonstrate its capability to quantitatively distinguish protein aggregates and silicone oil in the presence of varying amounts of the surfactants SDS and polysorbate 80 in the size range of 0.5-10 μm without the need for dilution or special sample preparation. We show that SDS denatures proteins and stabilizes silicone oil. We also show that polysorbate 80 may limit protein aggregate formation if it is added to an IgG solution before introducing silicone oil.
在存在硅油的情况下对蛋白质聚集体进行特征描述，这对制药行业来说是一个长期存在的挑战。硅油常被用作输送和储存治疗性蛋白产品的设备中的润滑剂，并且与蛋白质聚集有关，这可能会降低药物的有效性或在患者中引起自身免疫反应。大多数传统技术无法在其原始配方中对小于 5μm 的尺寸的蛋白质聚集体和硅油进行定量区分。我们使用全息视频显微镜研究蛋白质聚集，以证明其能够在不同浓度的表面活性剂 SDS 和聚山梨酯 80 的存在下，在 0.5-10μm 的范围内对蛋白质聚集体和硅油进行定量区分，而无需稀释或特殊的样品制备。我们表明 SDS 使蛋白质变性并稳定硅油。我们还表明，如果在引入硅油之前将聚山梨酯 80 添加到 IgG 溶液中，则可能会限制蛋白质聚集体的形成。
