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Peer-reviewedCC BY 4.0Polymers

Choline Chloride/Lactic Acid Natural Deep Eutectic Solvent: A Multifunctional Tool for the Preparation of Chitosan Nanoparticles and Hybrid Nanocomposite Xanthan Gum Eutectogels

  1. 1Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15772 Athens, Greece
  2. 2Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, School of Health and Caring Sciences, University of West Attica, 12243 Athens, Greece

Abstract

In this work, an innovative hybrid eutectogel-chitosan nanoparticles system was developed, suitable for biomedical applications. Chitosan (CS) was used as a matrix for the encapsulation of the naturally occurring flavonoid chrysin (Chr), known for its significant biological activities but with limited applications due to its very low aqueous solubility resulting in poor oral bioavailability. A natural deep eutectic solvent (NADES), namely choline chloride/lactic acid at a 1:2 molar ratio, was used as a multifunctional component in the preparation of chitosan nanoparticles (CS-NPs) for chrysin encapsulation, facilitating nanoparticle formation under the investigated conditions. The hydrodynamic diameter of the CS-Chr NPs was 138.8 nm, as determined using nanoparticle tracking analysis, with a high positive ζ-potential of +46.53 mV. The encapsulation efficiency of the CS-Chr NPs was 45%. CS-Chr NPs and blank-CS NPs were evaluated for their hemolytic properties and demonstrated hemolytic activity, within the limits of allowed nanotoxicity (hemolysis < 5%). Additionally, the NADES acted as a matrix, with xanthan gum functioning as a gelator, for the preparation of eutectogels. The resulting eutectogel was developed to combine the advantages of the NADES-based environment and chitosan–chrysin nanoparticles (CS–Chr NPs) with the structural integrity and prolonged retention provided by a gel matrix, thereby offering a stable and versatile platform for the localized delivery of chrysin. The prepared xanthan gum eutectogels showed significant swelling ratio capacity (120%) even after the swollen sample was kept in the aqueous HCl solution (pH 1.2) for 3 h, indicating a good stability of the network. The release of chrysin from CS-Chr NPs reached 94% after 8 h, and exhibited predominantly Fickian diffusion (n = 0.4099). Incorporation of the CS-Chr NPs into the xanthan-gum-based eutectogel resulted in a more sustained chrysin release (76% after 8 h). The eutectogel release was predominantly diffusion-driven (Higuchi, R2 = 0.9796), with anomalous transport (n = 0.7247) indicating an additional contribution of polymer relaxation and/or swelling. The proposed NADES-based platform provides a sustainable strategy for the development of multifunctional nanocomposite eutectogels, combining biocompatible components with the unique functional properties of natural deep eutectic solvents for advanced biomedical delivery applications.

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BibTeX
@article{pitterou2026choline,
  title = {{Choline Chloride/Lactic Acid Natural Deep Eutectic Solvent: A Multifunctional Tool for the Preparation of Chitosan Nanoparticles and Hybrid Nanocomposite Xanthan Gum Eutectogels}},
  author = {Ioanna Pitterou and Kyriakos Kyriakopoulos and Maria-Aspasia Kosma and Evangelos Meletis and Andromachi Tzani and Sotirios P. Fortis and Anastasios G. Kriebardis and Anastasia Detsi},
  journal = {Polymers},
  year = {2026},
  month = oct,
  doi = {10.3390/polym18202502},
  url = {https://www.mdpi.com/2073-4360/18/20/2502},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Choline Chloride/Lactic Acid Natural Deep Eutectic Solvent: A Multifunctional Tool for the Preparation of Chitosan Nanoparticles and Hybrid Nanocomposite Xanthan Gum Eutectogels
AU  - Ioanna Pitterou
AU  - Kyriakos Kyriakopoulos
AU  - Maria-Aspasia Kosma
AU  - Evangelos Meletis
AU  - Andromachi Tzani
AU  - Sotirios P. Fortis
AU  - Anastasios G. Kriebardis
AU  - Anastasia Detsi
PY  - 2026
DA  - 2026/10/01
JO  - Polymers
DO  - 10.3390/polym18202502
UR  - https://www.mdpi.com/2073-4360/18/20/2502
AB  - In this work, an innovative hybrid eutectogel-chitosan nanoparticles system was developed, suitable for biomedical applications. Chitosan (CS) was used as a matrix for the encapsulation of the naturally occurring flavonoid chrysin (Chr), known for its significant biological activities but with limited applications due to its very low aqueous solubility resulting in poor oral bioavailability. A natural deep eutectic solvent (NADES), namely choline chloride/lactic acid at a 1:2 molar ratio, was used as a multifunctional component in the preparation of chitosan nanoparticles (CS-NPs) for chrysin encapsulation, facilitating nanoparticle formation under the investigated conditions. The hydrodynamic diameter of the CS-Chr NPs was 138.8 nm, as determined using nanoparticle tracking analysis, with a high positive ζ-potential of +46.53 mV. The encapsulation efficiency of the CS-Chr NPs was 45%. CS-Chr NPs and blank-CS NPs were evaluated for their hemolytic properties and demonstrated hemolytic activity, within the limits of allowed nanotoxicity (hemolysis < 5%). Additionally, the NADES acted as a matrix, with xanthan gum functioning as a gelator, for the preparation of eutectogels. The resulting eutectogel was developed to combine the advantages of the NADES-based environment and chitosan–chrysin nanoparticles (CS–Chr NPs) with the structural integrity and prolonged retention provided by a gel matrix, thereby offering a stable and versatile platform for the localized delivery of chrysin. The prepared xanthan gum eutectogels showed significant swelling ratio capacity (120%) even after the swollen sample was kept in the aqueous HCl solution (pH 1.2) for 3 h, indicating a good stability of the network. The release of chrysin from CS-Chr NPs reached 94% after 8 h, and exhibited predominantly Fickian diffusion (n = 0.4099). Incorporation of the CS-Chr NPs into the xanthan-gum-based eutectogel resulted in a more sustained chrysin release (76% after 8 h). The eutectogel release was predominantly diffusion-driven (Higuchi, R2 = 0.9796), with anomalous transport (n = 0.7247) indicating an additional contribution of polymer relaxation and/or swelling. The proposed NADES-based platform provides a sustainable strategy for the development of multifunctional nanocomposite eutectogels, combining biocompatible components with the unique functional properties of natural deep eutectic solvents for advanced biomedical delivery applications.
SN  - 2073-4360
ER  -