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Immunotoxicity Testing of Nanomedicinal Products: Possible Pitfalls in Endotoxin Determination

[ Vol. 2 , Issue. 2 ]


Christina Giannakou, Robert E. Geertsma, Wim H. de Jong, Henk van Loveren, Rob J. Vandebriel and Margriet VDZ Park   Pages 95 - 102 ( 8 )


Nanomaterials (NMs) find application in the biomedical and pharmaceutical area, the so-called nanomedicinal products (NMPs). Once in the body, NMPs tend to end up in cells of the immune system. Due to reported adverse effects on the immune system after NMPs administration, the immunotoxicity profile of these products should be investigated. Information on the endotoxin levels in NMs and NMPs is crucial for an appropriate interpretation of toxicity results, especially regarding immunotoxicity assays. The aim of this review was to identify the assays that are available today for endotoxin determination in NMs and NMPs and possible pitfalls as a result of the interaction of the testing samples with the assays. Many of the currently available assays to determine endotoxin contamination were found to have limited compatibility with NMs and NMPs due to interference, which is mostly related to their absorbance or fluorescence properties and their strong tendency to adsorb biomolecules such as LPS and assay reagents to their surface. Such interference of NMs and NMPs is not unique to endotoxin determination assays but is also observed with various toxicity assays. Regarding the above, the availability of an assay to test endotoxin presence without nanospecific interference is essential. In the meantime, use of appropriate assay controls, producing and handling the NMs and NMPs in an endotoxin-free environment may be part of the solution. In the absence of a single competent assay, it is more likely that a testing strategy of multiple currently available assays will give reliable results.


Endotoxin, immunotoxicity, testing, assessment, lipopolysaccharide, interference, nanomedicines.


Department of Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

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