Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21702, USA.
Molecules. 2020 Jul 24;25(15):3367. doi: 10.3390/molecules25153367.
Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. Pyrogenicity (the ability to induce fever) and activation of innate immune responses underlying both acute toxicities (e.g., anaphylactoid reactions or pseudoallergy, cytokine storm) and long-term effects (e.g., immunogenicity) are among the IMAE commonly related to IIMI contamination. Endotoxins of gram-negative bacteria are the best-studied IIMIs in that both methodologies for and pitfalls in their detection and quantification are well established. Additionally, regulatory guidance documents and research papers from laboratories worldwide are available on endotoxins. However, less information is currently known about other IIMIs. Herein, we focus on one such IIMI, namely, beta-glucans, and review literature and discuss the experience of the Nanotechnology Characterization Lab (NCL) with the detection of beta-glucans in nanotechnology-based drug products.
了解药物产品中固有免疫调节杂质 (IIMIs) 的潜在污染对于建立其安全性概况至关重要。IIMIs 是一类具有多种组成和结构的分子，它们会导致药物产品的免疫介导的不良反应 (IMAE)。热原性（引起发热的能力）和固有免疫反应的激活是与 IIMI 污染相关的 IMAE 的常见类型，包括急性毒性（例如类过敏反应或假性过敏、细胞因子风暴）和长期效应（例如免疫原性）。革兰氏阴性菌的内毒素是研究最充分的 IIMIs，因为其检测和定量的方法以及陷阱都已经得到很好的建立。此外，关于内毒素的监管指导文件和来自世界各地实验室的研究论文也有提供。然而，目前对于其他 IIMIs 的了解较少。在此，我们专注于一种这样的 IIMI，即β-葡聚糖，并综述文献并讨论纳米技术特征化实验室 (NCL) 在检测基于纳米技术的药物产品中的β-葡聚糖方面的经验。
