Toxicological profiling of nutraceutical-grade curcumin-loaded solid lipid nanoparticles using Caco-2 cells and zebrafish (Danio rerio) embryo models

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. • SLN_curc and SLNs kept Caco-2 viability >80%; while free curcumin reduced it. • SLN_curc and free curcumin caused embryo death at ≥15 μg·mL −1 , while SLN were toxic at 50 μg·mL −1 . • SLN_curc had no sublethal toxicity below 5 μg·mL −1 in zebrafish embryos. • Zebrafish embryos are an effective in vivo model for screening nanotoxicity.