Dépôt numérique

Drug Self-Aggregation into Nano-Entities Has the Potential to Induce Immune Responses

Shahout, Fatma; Vanharen, Marion; Saafane, Abdelaziz; Gillard, James; Girard, Denis ORCID logoORCID: https://orcid.org/0000-0002-3342-5027 et Laplante, Steven ORCID logoORCID: https://orcid.org/0000-0003-2835-5789 (2023). Drug Self-Aggregation into Nano-Entities Has the Potential to Induce Immune Responses Molecular pharmaceutics , vol. 20 , nº 8. pp. 4031-4040. DOI: 10.1021/acs.molpharmaceut.3c00196.

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The free-state solution behaviors of small molecules profoundly affect their respective properties. It is becoming more obvious that compounds can adopt a three-phase equilibrium when placed in an aqueous solution, among soluble-lone molecule form, self-assembled aggregate form (nano-entities), and solid precipitate form. Recently, correlations have emerged between the existence of self-assemblies into drug nano-entities and unintended side effects. This report describes our pilot study involving a selection of drugs and dyes to explore if there may be a correlation between the existence of drug nano-entities and immune responses. We first implement practical strategies for detecting the drug self-assemblies using a combination of nuclear magnetic resonance (NMR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and confocal microscopy. We then used enzyme-linked immunosorbent assays (ELISA) to monitor the modulation of immune responses on two cellular models, murine macrophage and human neutrophils, upon exposure to the drugs and dyes. The results suggest that exposure to some aggregates correlated with an increase in IL-8 and TNF-α in these model systems. Given this pilot study, further correlations merit pursuing on a larger scale given the importance and potential impact of drug-induced immune-related side effects.

Type de document: Article
Mots-clés libres: free-state solution behaviors; immune responses; nano-entities; side effects; three-phase equilibrium.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 déc. 2023 18:08
Dernière modification: 09 déc. 2023 18:08
URI: https://espace.inrs.ca/id/eprint/13674

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