用受激拉曼散射成像表征硅油诱导的蛋白质聚集

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Brian Wong, Xi Zhao*, Yongchao Su, Hanlin Ouyang, Timothy Rhodes, Wei Xu, Hanmi Xi and Dan Fu*, 
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引用次数: 0

摘要

生物制药产品中的颗粒对产品的质量和安全具有很大的危害。药物中颗粒的鉴定和定量对于了解颗粒形成机制具有重要意义,有助于在制剂开发和生产过程中制定颗粒形成的控制策略。然而,现有的微流成像和光遮蔽测量等分析技术缺乏检测小于2 μm颗粒的灵敏度和分辨率。更重要的是,这些技术不能提供化学信息来确定颗粒的组成。在这项工作中,我们通过应用受激拉曼散射(SRS)显微镜技术来监测在预填充的注射器桶中形成的蛋白质颗粒和硅油滴的C-H拉曼拉伸模式来克服这些挑战。通过比较各组分的相对信号强度和光谱特征,大多数颗粒可归类为蛋白质-硅油聚集体。我们进一步表明,形态特征是颗粒组成的不良指标。我们的方法能够以无标记的方式,用化学和空间信息量化蛋白质治疗中的聚集,有可能实现高通量筛选或聚集机制的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging

Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging

Particles in biopharmaceutical products present high risks due to their detrimental impacts on product quality and safety. Identification and quantification of particles in drug products are important to understand particle formation mechanisms, which can help develop control strategies for particle formation during the formulation development and manufacturing process. However, existing analytical techniques such as microflow imaging and light obscuration measurement lack the sensitivity and resolution to detect particles with sizes smaller than 2 μm. More importantly, these techniques are not able to provide chemical information to determine particle composition. In this work, we overcome these challenges by applying the stimulated Raman scattering (SRS) microscopy technique to monitor the C–H Raman stretching modes of the proteinaceous particles and silicone oil droplets formed in the prefilled syringe barrel. By comparing the relative signal intensity and spectral features of each component, most particles can be classified as protein–silicone oil aggregates. We further show that morphological features are poor indicators of particle composition. Our method has the capability to quantify aggregation in protein therapeutics with chemical and spatial information in a label-free manner, potentially allowing high throughput screening or investigation of aggregation mechanisms.

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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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