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Toxicological profiling of nutraceutical-grade curcumin-loaded solid lipid nanoparticles using Caco-2 cells and
Raquel F S Gonçalves1, Joana Ribeiro2, Joana T Martins1
1CEB - Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; LABBELS - Associate Laboratory, Braga, Guimarães, Portugal.
Abstract:
The development of bio-based nanostructures to encapsulate bioactive compounds represents a promising approach for creating functional foods with improved nutritional and health benefits. However, their regular dietary use raises safety concerns, even when using food-grade ingredients. This study aimed to evaluate the toxicity of curcumin-loaded solid lipid nanoparticles (SLN_curc) through in vitro assays with Caco-2 cells and in vivo assays with zebrafish embryos (Danio rerio). In vitro, free curcumin reduced Caco-2 viability to slightly below 80% across all (nominal) tested concentrations, while both SLN and SLN_curc maintained cell viability above 80%, suggesting no cytotoxicity. In vivo, free curcumin and SLN_curc caused high mortality at the highest (nominal) concentrations, and SLN alone induced over 75% lethality at 50 μg·mL-1, indicating that curcumin itself strongly contributes to acute toxicity above 5 μg·mL-1. Nonetheless, SLN and SLN_curc produced significant concentration-dependent effects on most sub-lethal parameters, though SLN_curc exhibited no significant sub-lethal toxicity at (nominal) concentrations below 5 μg·mL-1. Overall, curcumin-loaded SLNs demonstrated a safe profile at lower (nominal) concentrations, supporting their potential in functional foods and supplements. Moreover, zebrafish embryos proved to be a valuable alternative vertebrate model for high-throughput screening of nanostructures in food applications.

