Structural dynamics and environmental safety of thyme essential oil-based nanoemulsions : a look at nanoscale organization and ecotoxicological outcomes
(2026) In International Journal of Pharmaceutics 702.- Abstract
The development of stable, high-concentration oil-in-water nanoemulsions (NEs) incorporating thyme essential oil (TEO) is hindered by intrinsic instability mechanisms, such as Ostwald ripening, and by challenges in characterizing concentrated, optically complex systems. Here, a rational, inquiry-driven formulation strategy, aligned with Formulation by Design principles, was applied to produce NEs containing 25% w/w oil phase. By systematically evaluating surfactant type, HLB, and the incorporation of neem oil as a ripening inhibitor, three stable formulations (TT80, TNT80, and TL) were obtained with reduced surfactant content and enhanced structural stability. Dilution effects were investigated using DLS, NTA, and small-angle X-ray... (More)
The development of stable, high-concentration oil-in-water nanoemulsions (NEs) incorporating thyme essential oil (TEO) is hindered by intrinsic instability mechanisms, such as Ostwald ripening, and by challenges in characterizing concentrated, optically complex systems. Here, a rational, inquiry-driven formulation strategy, aligned with Formulation by Design principles, was applied to produce NEs containing 25% w/w oil phase. By systematically evaluating surfactant type, HLB, and the incorporation of neem oil as a ripening inhibitor, three stable formulations (TT80, TNT80, and TL) were obtained with reduced surfactant content and enhanced structural stability. Dilution effects were investigated using DLS, NTA, and small-angle X-ray scattering (SAXS), demonstrating that conventional characterization techniques may introduce artifacts when applied to highly concentrated systems without accounting for compositional and structural changes. Dilution tests elucidated the transition from concentrated to diluted states, providing insight into measurement constraints an4d potential application scenarios. Among the tested systems, TL exhibited the highest structural resistance upon dilution. Ecotoxicological assessment using Scenedesmus sp. and Daphnia magna revealed species-specific and endpoint-dependent responses, underscoring the importance of a multi-species approach for environmental risk evaluation. At concentrations below 10 mg/L, the NEs showed minimal ecological impact, suggesting that the formulations could be effective while remaining environmentally safe, thus supporting their potential use in multiple fields, including pharmaceutical applications aligned with green pharmacy principles, as well as food and agricultural sectors, such as compost biostabilisation. Overall, this work establishes a methodological and application-oriented framework for the rational design of concentrated, environmentally conscious NEs, and provides new insights into the relationships between formulation composition, nanostructure, stability, and ecotoxicological behavior.
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- author
- Fabiano, Maria Gioia LU ; D'Intino, Eleonora ; Stacchini, Francesca Romana ; Cedervall, Tommy LU ; Ekvall, Mikael LU ; Ricci, Caterina ; Garzoli, Stefania ; Marianecci, Carlotta and Carafa, Maria
- organization
- publishing date
- 2026-09-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Daphnia magna, Ecotoxicity, Nanoemulsions, Neem oil, Ostwald ripening, Physicochemical characterization, Thyme essential oil
- in
- International Journal of Pharmaceutics
- volume
- 702
- article number
- 127204
- pages
- 14 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:42492641
- scopus:105045671597
- ISSN
- 0378-5173
- DOI
- 10.1016/j.ijpharm.2026.127204
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026 The Author(s)
- id
- 83ca8357-83aa-4a55-a5ea-76c04eb0577e
- date added to LUP
- 2026-08-18 13:49:30
- date last changed
- 2026-09-01 14:44:56
@article{83ca8357-83aa-4a55-a5ea-76c04eb0577e,
abstract = {{<p>The development of stable, high-concentration oil-in-water nanoemulsions (NEs) incorporating thyme essential oil (TEO) is hindered by intrinsic instability mechanisms, such as Ostwald ripening, and by challenges in characterizing concentrated, optically complex systems. Here, a rational, inquiry-driven formulation strategy, aligned with Formulation by Design principles, was applied to produce NEs containing 25% w/w oil phase. By systematically evaluating surfactant type, HLB, and the incorporation of neem oil as a ripening inhibitor, three stable formulations (TT80, TNT80, and TL) were obtained with reduced surfactant content and enhanced structural stability. Dilution effects were investigated using DLS, NTA, and small-angle X-ray scattering (SAXS), demonstrating that conventional characterization techniques may introduce artifacts when applied to highly concentrated systems without accounting for compositional and structural changes. Dilution tests elucidated the transition from concentrated to diluted states, providing insight into measurement constraints an4d potential application scenarios. Among the tested systems, TL exhibited the highest structural resistance upon dilution. Ecotoxicological assessment using Scenedesmus sp. and Daphnia magna revealed species-specific and endpoint-dependent responses, underscoring the importance of a multi-species approach for environmental risk evaluation. At concentrations below 10 mg/L, the NEs showed minimal ecological impact, suggesting that the formulations could be effective while remaining environmentally safe, thus supporting their potential use in multiple fields, including pharmaceutical applications aligned with green pharmacy principles, as well as food and agricultural sectors, such as compost biostabilisation. Overall, this work establishes a methodological and application-oriented framework for the rational design of concentrated, environmentally conscious NEs, and provides new insights into the relationships between formulation composition, nanostructure, stability, and ecotoxicological behavior.</p>}},
author = {{Fabiano, Maria Gioia and D'Intino, Eleonora and Stacchini, Francesca Romana and Cedervall, Tommy and Ekvall, Mikael and Ricci, Caterina and Garzoli, Stefania and Marianecci, Carlotta and Carafa, Maria}},
issn = {{0378-5173}},
keywords = {{Daphnia magna; Ecotoxicity; Nanoemulsions; Neem oil; Ostwald ripening; Physicochemical characterization; Thyme essential oil}},
language = {{eng}},
month = {{09}},
publisher = {{Elsevier}},
series = {{International Journal of Pharmaceutics}},
title = {{Structural dynamics and environmental safety of thyme essential oil-based nanoemulsions : a look at nanoscale organization and ecotoxicological outcomes}},
url = {{http://dx.doi.org/10.1016/j.ijpharm.2026.127204}},
doi = {{10.1016/j.ijpharm.2026.127204}},
volume = {{702}},
year = {{2026}},
}