RT info:eu-repo/semantics/article
T1 A three-tier in silico toxicology framework for formulated essential-oil nanocapsules: integrating molecular hazard, release kinetics and nano-bioavailability for safe-and-sustainable-by-design assessment
A1 Huerta Sainz, Sergio de la
A1 Diez Cabanes, Valentin
A1 Gutiérrez Vega, Alberto
A1 Martel Martín, Sonia
A1 Fernández Pampín, Natalia
A1 Rumbo Lorenzo, Carlos
A1 Marcos Villa, Pedro A.
A1 Bol Arreba, Alfredo
A1 Marson, Domenico
A1 Laurini, Erik
A1 Aparicio Martínez, Santiago
K1 Essential oil nanocapsules
K1 Systems toxicology
K1 Integrated hazard prediction
K1 Korsmeyer Peppas release kinetics
K1 Safe and sustainable by design
K1 Human and environmental health
K1 Esencias y aceites esenciales
K1 Essences and essential oils
K1 Química
K1 Chemistry
AB Essential-oil nanocapsules are bio-based antimicrobial formulations central to agri-food sustainability, yet their human and environmental hazard as formulated products cannot be assessed by conventional molecular QSAR, which ignores controlled release kinetics, nano-specific bio-interactions, and shell-material contributions. We apply a systems toxicology approach — integrating molecular QSAR (Tier 1), Korsmeyer–Peppas release kinetics (Tier 2), and a nano-specific bioavailability correction layer (Tier 3) — to produce the first quantitative integrated hazard prediction for two clove-oil advanced-material (AdMa) nanocapsule formulations: AdMa EO@PEC-GEL (pectin–gelatin shell, CaCl₂ crosslinker) and AdMa EO@Chi (chitosan shell, formaldehyde crosslinker).Eugenol (∼90 wt% core) is the principal toxicophore. Release parameters were scaled from published eugenol–chitosan kinetic data to the 1 μm target particle size; nano-correction factors were calibrated from published surface-charge and uptake relationships. The integrated model predicts AdMa EO@PEC-GEL to be 9.1× safer than free eugenol (IC₅₀ ∼3.5 mM vs. 0.38 mM), driven by anionic surface charge and 80% encapsulation efficiency. AdMa EO@Chi retains toxicity close to the free molecule (IC₅₀ ∼0.91 mM; 2.4×) because cationic surface charge offsets the encapsulation benefit. The formaldehyde crosslinker introduces independent sensitisation, genotoxicity, and IARC Group 1 carcinogenicity flags — quantified via the concentration-addition mixture model — entirely absent from PEC-GEL.Sensitivity analysis identifies zeta potential as the dominant model uncertainty driver. Tier 2 is retrospectively validated against published release kinetics (R2 = 0.997). The Korsmeyer–Peppas tier applies directly to environmental fate scenarios — pH-dependent shell dissolution in soil and aquatic compartments — providing a unified architecture for human–environment integrated hazard assessment aligned with planetary health priorities. An interactive, browser-based digital twin is provided as Supplementary Information: it recomputes all integrated predictions in real time as the user adjusts the model inputs (zeta potential, particle size, encapsulation efficiency, eugenol fraction, release time and pH/enzyme condition), enabling transparent scenario analysis and progressive refinement as experimental data become available, in line with the iterative Safe-and-Sustainable-by-Design (SSbD) workflow.
PB Elsevier
SN 2468-1113
YR 2026
FD 2026-09
LK https://hdl.handle.net/10259/11987
UL https://hdl.handle.net/10259/11987
LA eng
NO This work was funded by SUNRISE project (HORIZON-EU, HORIZON-CL4-2023-RESILIENCE-01- SUNRISE-GA 101137324).
DS Repositorio Institucional de la Universidad de Burgos
RD 06-sep-2026