Vandebriel, Rob J, David, Christopher AW 
ORCID: 0000-0001-8504-2354, Vermeulen, Jolanda P and Liptrott, Neill J ORCID: 0000-0002-5980-8966
(2022)
An inter-laboratory comparison of an NLRP3 inflammasome activation assay and dendritic cell maturation assay using a nanostructured lipid carrier and a polymeric nanomedicine, as exemplars.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 12 (9).
pp. 2225-2242.
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DDTR-D-22-00024_R1.pdf - Author Accepted Manuscript Download (6MB) | Preview |
Abstract
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-1β 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NLRP3 inflammasome activation, Monocyte-derived dendritic cell, Dendritic cell maturation, Nanostructured lipid carrier, Polymeric nanomedicine, Inter-laboratory comparison |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Apr 2022 08:03 |
| Last Modified: | 18 Jan 2023 21:04 |
| DOI: | 10.1007/s13346-022-01206-6 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3153460 |
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