Journal
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
Volume 12, Issue 9, Pages 2225-2242Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s13346-022-01206-6
Keywords
NLRP3 inflammasome activation; Monocyte-derived dendritic cell; Dendritic cell maturation; Nanostructured lipid carrier; Polymeric nanomedicine; Inter-laboratory comparison
Funding
- European Union [761104]
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Nanoparticles, including nanomedicines, interact with the immune system and affect immune mechanisms like NLRP3 inflammasome activation and DC maturation. Two nanomedicines were evaluated for their effects on these mechanisms, and inter-laboratory comparison demonstrated reproducible results.
Nanoparticles including nanomedicines are known to be recognised by and interact with the immune system. As these interactions may result in adverse effects, for safety evaluation, the presence of such interactions needs to be investigated. Nanomedicines in particular should not unintendedly interact with the immune system, since patient's exposure is not minimised as in the case of 'environmental' nanoparticles, and repeated exposure may be required. NLRP3 inflammasome activation and dendritic cell (DC) maturation are two types of immune mechanisms known to be affected by nanoparticles including nanomedicines. NLRP3 inflammasome activation results in production of the pro-inflammatory cytokines IL-1 beta and IL-18, as well as a specific type of cell death, pyroptosis. Moreover, chronic NLRP3 inflammasome activation has been related to several chronic diseases. Upon maturation, DC activate primary T cells; interference with this process may result in inappropriate activation and skewing of the adaptive immune response. Here, we evaluated the effect of two nanomedicines, representing nanostructured lipid carriers and polymers, on these two assays. Moreover, with a view to possible future standardisation and regulatory application, these assays were subject to an inter-laboratory comparison study using common SOPs. One laboratory performed three independent NLRP3 inflammasome activation experiments, while the other performed a single experiment. Two laboratories each performed three independent DC maturation experiments. While the nanostructured lipid carrier only showed marginal effects, the polymers showed major cytotoxicity. No evidence for inflammasome activation or DC maturation was demonstrated. Intra- and inter-laboratory comparison showed clearly reproducible results.
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