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

Giannakou, Christina; Park, Margriet V. D. Z.; Jong, Wim H. de; Loveren, Henk Van; Vandebriel, Rob J.; Geertsma, Robert E.

doi:10.2147/ijn.s102385

Cited by 61 publications

(43 citation statements)

References 110 publications

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“…Acute adverse immunological effects (hypersensitivity) are a known safety aspect associated with NMPs, and although physicians generally adapt their treatment protocols to anticipate such responses more insight and a validated test strategy to predict these effects may contribute in enabling the prevention of hypersensitivity responses to NMPs. For recommendations, for immunotoxicity testing of NMPs, we refer to our recent publication by Giannakou et al 45 …”

Section: Resultsmentioning

confidence: 99%

“…However, it is uncertain whether this procedure provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. 45 Compared to small molecular entities, the immune system acts to eliminate or interact with NPs to a greater extent, and therefore, immunotoxicity is an end point of specific interest with respect to NP-specific toxicity. 46,47 The accumulation of iron NPs in organs of the reticuloendothelium system (eg, the spleen), for instance, can induce adverse health effects by disturbing immune homeostasis, 48 and the formation of protein coronas could modulate the immune response.…”

Section: Discussionmentioning

confidence: 99%

“…49 A recent comparison between current regulatory testing requirements and the accumulating knowledge on immunotoxic effects of NMPs showed that specific immunotoxic effects associated with NMPs, such as complement activation-related pseudo-allergy (CARPA), myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. 45 Our first objective was to investigate whether specific toxicity could be related to certain structural types of NMPs. Overall, the data from our survey on the toxicity of NMPs do not indicate that certain toxic effects, in terms of specific end points, are associated with specific groups or structural types of NMPs; however, the numbers of NMPs analyzed per group of NMPs were small.…”

Section: Discussionmentioning

confidence: 99%

“…36 The importance of such mechanisms should be further studied, and the immunotoxicological effects of NMPs should be more accurately evaluated by an expanded testing strategy, which is equipped to stratify applicable testing for the various types of NMPs. 45 Our survey using publicly available toxicity information and comparing five sets of drugs presents a first attempt to obtain insights into the side effects specific for NMPs. As more information will become available, more such comparisons can be made and possibly broader conclusions could be drawn.…”

Section: Discussionmentioning

confidence: 99%

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Nanomedicinal products: a survey on specific toxicity and side effects

Brand¹,

Noorlander²,

Giannakou³

et al. 2017

IJN

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Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Nanomedicinal products: a survey on specific toxicity and side effects

Brand¹,

Noorlander²,

Giannakou³

et al. 2017

IJN

Self Cite

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“…One example of this can be seen in the development of immunotoxicology testing protocols between 1980 and present (Vos 1980;Dietert 2010;Giannakou et al 2016). However, as described by Dietert and Silbergeld (2015), what has been missing from most safety testing models is the consideration of the complete human-mammal plus the human microbiome (i.e., the human superorganism).…”

Section: Re-envisioning Human Environmental Health Risksmentioning

confidence: 99%

Safety and risk assessment for the human superorganism

Dietert

2017

Human and Ecological Risk Assessment: An International Journal

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This editorial on safety evaluation and risk assessment for the human superorganism introduces a series of papers arguing for a fundamental shift in how we approach human health risk assessment. In this series emphasis is placed on the risk of infectious disease. Our 21 st st century understanding of human biology is that, as holobionts, we possess a majority of microbial cells and genes. In fact, our microbes fundamentally affect our interactions with the external environment, metabolism, physiology, and risk of both pathology and disease. As holobionts, we require our microbial partners for us to be both complete and healthy. Using the 20 th century understanding of human biology, we failed to capture the effects of the microbiome in evaluating health risks. But 21 st century risk assessments such as those associated with exposure to specific microbial pathogens need to include the human microbiome. Microbiome status will be central in determining the health risks for both individuals and populations.

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