Frontiers of Materials Science

, Volume 12, Issue 1, pp 83–94 | Cite as

Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

  • Amina Ben Mihoub
  • Boubakeur Saidat
  • Youssef Bal
  • Céline Frochot
  • Régis Vanderesse
  • Samir Acherar
Research Article


In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD-g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA/β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA):w(β-CD-g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.


β-cyclodextrin-grafted chitosan hyaluronic acid ionic gelation drug delivery physicochemical parameters control 


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A.B.M. was supported by the Algerian Ministry of Higher Education and Scientific Research scholarship (No: 115/PNE: 2016/2017). The authors acknowledge the Dr. Benoît Frisch and Maria-Vittoria Spanedda (« Laboratoire de Conception et Application de Molécules Bioactives » UMR7199, Équipe de biovectorologie, Strasbourg) for nanoparticles characterizations.


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Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Amina Ben Mihoub
    • 1
    • 2
  • Boubakeur Saidat
    • 2
  • Youssef Bal
    • 3
    • 4
  • Céline Frochot
    • 5
  • Régis Vanderesse
    • 1
  • Samir Acherar
    • 1
  1. 1.Laboratoire de Chimie Physique Macromoléculaire (LCPM)Université de Lorraine-CNRS, UMR 7375Nancy CedexFrance
  2. 2.Laboratory of Physical Chemistry of Materials (LPCM)Faculty of Sciences, (UATL)LaghouatAlgeria
  3. 3.Laboratory of Biomaterials & Transport Phenomena (LBTP)MedeaAlgeria
  4. 4.Department of Chemistry, Faculty of SciencesUniversity Saéd Dahleb of Blida (USDB)BlidaAlgeria
  5. 5.Laboratoire Réactions et Génie des Procédés (LRGP)Université de Lorraine-CNRS, UMR 7274Nancy CedexFrance

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