A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht...

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Autores principales:	Giannakou C, Park MV, de Jong WH, van Loveren H, Vandebriel RJ, Geertsma RE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Nanomedicine regulatory requirements safety testing methods immunotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/493e28286387461b99d83869c77d6d7d
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spelling	oai:doaj.org-article:493e28286387461b99d83869c77d6d7d2021-12-02T01:46:43ZA comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements1178-2013https://doaj.org/article/493e28286387461b99d83869c77d6d7d2016-06-01T00:00:00Zhttps://www.dovepress.com/a-comparison-of-immunotoxic-effects-of-nanomedicinal-products-with-reg-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs. Keywords: nanomedicine, regulatory requirements, safety, testing methods, immunotoxicityGiannakou CPark MVde Jong WHvan Loveren HVandebriel RJGeertsma REDove Medical PressarticleNanomedicineregulatory requirementssafetytesting methodsimmunotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2935-2952 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanomedicine regulatory requirements safety testing methods immunotoxicity Medicine (General) R5-920
spellingShingle	Nanomedicine regulatory requirements safety testing methods immunotoxicity Medicine (General) R5-920 Giannakou C Park MV de Jong WH van Loveren H Vandebriel RJ Geertsma RE A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
description	Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs. Keywords: nanomedicine, regulatory requirements, safety, testing methods, immunotoxicity
format	article
author	Giannakou C Park MV de Jong WH van Loveren H Vandebriel RJ Geertsma RE
author_facet	Giannakou C Park MV de Jong WH van Loveren H Vandebriel RJ Geertsma RE
author_sort	Giannakou C
title	A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
title_short	A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
title_full	A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
title_fullStr	A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
title_full_unstemmed	A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
title_sort	comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/493e28286387461b99d83869c77d6d7d
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A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

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