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Considerations and Some Practical Solutions to Overcome Nanoparticle Interference with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations

  • Barry W. Neun
  • Marina A. DobrovolskaiaEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1682)

Abstract

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.

Key words

Endotoxin LAL Interference Inhibition enhancement control 

Notes

Acknowledgment

This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Cancer Research Technology Program¸ Nanotechnology Characterization LaboratoryLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchFrederickUSA

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