Considerations and Some Practical Solutions to Overcome Nanoparticle Interference with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations
Considerations and Some Practical Solutions to Overcome Nanoparticle Interference with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations
复制标题
DOI：
10.1007/978-1-4939-7352-1_3
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Dobrovolskaia, Marina A.
中科院分区：
文献类型：
--
作者：
Neun, Barry W.;Dobrovolskaia, Marina A.
需要监测药物和医疗器械中的内毒素污染，以避免接受这些产品的患者发生热原反应和脓毒性休克。工程纳米材料和基于纳米技术的医疗产品的内毒素污染是一个重大的转化障碍。纳米颗粒经常干扰制药工业中常用的用于内毒素检测和定量的体外鲎变形细胞溶解物（LAL）测定。这种干扰挑战了含有工程纳米材料的纳米技术配制药物和医疗器械的临床前开发。之前已经报道了使用LAL测定法分析纳米颗粒的方案。在这里，我们讨论了选择LAL格式的考虑因素，并描述了一些实验方法，以克服纳米颗粒干扰的LAL测定，以获得更准确的估计内毒素污染的纳米技术为基础的产品。所讨论的方法不能解决所有类型的纳米颗粒干扰LAL测定，但可以用作解决该问题的起点。本章还描述了防止纳米技术配制产品中内毒素污染的方法。
Monitoring endotoxin contamination in drugs and medical devices is required to avoid pyrogenic response and septic shock in patients receiving these products. Endotoxin contamination of engineered nanomaterials and nanotechnology-based medical products represents a significant translational hurdle. Nanoparticles often interfere with an in vitro Limulus Amebocyte Lysate (LAL) assay commonly used in the pharmaceutical industry for the detection and quantification of endotoxin. Such interference challenges the preclinical development of nanotechnology-formulated drugs and medical devices containing engineered nanomaterials. Protocols for analysis of nanoparticles using LAL assays have been reported before. Here, we discuss considerations for selecting an LAL format and describe a few experimental approaches for overcoming nanoparticle interference with the LAL assays to obtain more accurate estimation of endotoxin contamination in nanotechnology-based products. The discussed approaches do not solve all types of nanoparticle interference with the LAL assays but could be used as a starting point to address the problem. This chapter also describes approaches to prevent endotoxin contamination in nanotechnology-formulated products.