Skip to main content
Log in

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

  • Research Article
  • Published:
Frontiers of Materials Science Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dey A, Koli U, Dandekar P, et al. Investigating behaviour of polymers in nanoparticles of chitosan oligosaccharides coated with hyaluronic acid. Polymer, 2016, 93: 44–52

    Article  Google Scholar 

  2. Al-Qadi S, Grenha A, Remuñán-López C. Chitosan and its derivatives as nanocarriers for siRNA delivery. Journal of Drug Delivery Science and Technology, 2012, 22(1): 29–42

    Article  Google Scholar 

  3. Al-Qadi S, Alatorre-Meda M, Zaghloul E M, et al. Chitosan–hyaluronic acid nanoparticles for gene silencing: The role of hyaluronic acid on the nanoparticles’ formation and activity. Colloids and Surfaces B: Biointerfaces, 2013, 103: 615–623

    Article  Google Scholar 

  4. Amidi M, Mastrobattista E, Jiskoot W, et al. Chitosan-based delivery systems for protein therapeutics and antigens. Advanced Drug Delivery Reviews, 2010, 62(1): 59–82

    Article  Google Scholar 

  5. Szejtli J. Introduction and general overview of cyclodextrin chemistry. Chemical Reviews, 1998, 98(5): 1743–1754

    Article  Google Scholar 

  6. Duchêne D, Bochot A. Thirty years with cyclodextrins. International Journal of Pharmaceutics, 2016, 514(1): 58–72

    Article  Google Scholar 

  7. Otero-Espinar F J, Torres-Labandeira J J, Alvarez-Lorenzo J C, et al. Cyclodextrins in drug delivery systems. Journal of Drug Delivery Science and Technology, 2010, 20(4): 289–301

    Article  Google Scholar 

  8. Zhang J, Ma P X. Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective. Advanced Drug Delivery Reviews, 2013, 65(9): 1215–1233

    Article  Google Scholar 

  9. Prabaharan M, Mano J F. Chitosan derivatives bearing cyclodextrin cavities as novel adsorbent matrices. Carbohydrate Polymers, 2006, 63(2): 153–166

    Article  Google Scholar 

  10. Zhang X G, Wu Z M, Gao X J, et al. Chitosan bearing pendant cyclodextrin as a carrier for controlled protein release. Carbohydrate Polymers, 2009, 77(2): 394–401

    Article  Google Scholar 

  11. Lu L, Shao X, Jiao Y, et al. Synthesis of chitosan-graft-β-cyclodextrin for improving the loading and release of doxorubicin in the nanoparticles. Journal of Applied Polymer Science, 2014, 131(21): 41034

    Article  Google Scholar 

  12. Yuan Z, Ye Y, Gao F, et al. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release. International Journal of Pharmaceutics, 2013, 446(1–2): 191–198

    Article  Google Scholar 

  13. Zhang H, Oh M, Allen C, et al. Monodisperse chitosan nanoparticles for mucosal drug delivery. Biomacromolecules, 2004, 5(6): 2461–2468

    Article  Google Scholar 

  14. Fan W, Yan W, Xu Z, et al. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids and Surfaces B: Biointerfaces, 2012, 90: 21–27

    Article  Google Scholar 

  15. Nasti A, Zaki N M, de Leonardis P, et al. Chitosan/TPP and chitosan/TPP-hyaluronic acid nanoparticles: systematic optimisation of the preparative process and preliminary biological evaluation. Pharmaceutical Research, 2009, 26(8): 1918–1930

    Article  Google Scholar 

  16. Jonassen H, Kjoniksen A L, Hiorth M. Effects of ionic strength on the size and compactness of chitosan nanoparticles. Colloid & Polymer Science, 2012, 290(10): 919–929

    Article  Google Scholar 

  17. Sawtarie N, Cai Y, Lapitsky Y. Preparation of chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity. Colloids and Surfaces B: Biointerfaces, 2017, 157: 110–117

    Article  Google Scholar 

  18. Gokce Y, Cengiz B, Yildiz N, et al. Ultrasonication of chitosan nanoparticle suspension: influence on particle size. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014, 462: 75–81

    Article  Google Scholar 

  19. Kedjarune-Leggat U, Supaprutsakul C, Chotigeat W. Ultrasound treatment increases transfection efficiency of low molecular weight chitosan in fibroblasts but not in KB cells. PLoS One, 2014, 9(3): e92076

    Article  Google Scholar 

  20. So M H, Ho C M, Chen R, et al. Hydrothermal synthesis of platinum-group-metal nanoparticles by using HEPES as a reductant and stabilizer. Chemistry — An Asian Journal, 2010, 5(6): 1322–1331

    Google Scholar 

  21. Stern R, Kogan G, Jedrzejas M J, et al. The many ways to cleave hyaluronan. Biotechnology Advances, 2007, 25(6): 537–557

    Article  Google Scholar 

  22. Sivadas N, O’Rourke D, Tobin A, et al. A comparative study of a range of polymeric microspheres as potential carriers for the inhalation of proteins. International Journal of Pharmaceutics, 2008, 358(1–2): 159–167

    Article  Google Scholar 

  23. Kalam M A. Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone. International Journal of Biological Macromolecules, 2016, 89: 127–136

    Article  Google Scholar 

  24. Li L, Qian Y, Jiang C, et al. The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds. Biomaterials, 2012, 33(12): 3428–3445

    Article  Google Scholar 

  25. Lokeshwar V B, Mirza S, Jordan A. Targeting hyaluronic acid family for cancer chemoprevention and therapy. Advances in Cancer Research, 2014, 123: 35–65

    Article  Google Scholar 

  26. Mok H, Park J W, Park T G. Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition. Bioconjugate Chemistry, 2007, 18(5): 1483–1489

    Article  Google Scholar 

  27. Melton L D, Slessor K N. Synthesis of monosubstituted cyclohexaamyloses. Carbohydrate Research, 1971, 18(1): 29–37

    Article  Google Scholar 

  28. Gonil P, Sajomsang W, Ruktanonchai U R, et al. Novel quaternized chitosan containing β-cyclodextrin moiety: Synthesis, characterization and antimicrobial activity. Carbohydrate Polymers, 2011, 83(2): 905–913

    Article  Google Scholar 

  29. Kievit F M, Wang F Y, Fang C, et al. Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro. Journal of Controlled Release, 2011, 152(1): 76–83

    Article  Google Scholar 

  30. Ji J, Hao S, Liu W, et al. Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study. Colloids and Surfaces B: Biointerfaces, 2011, 83(1): 103–107

    Article  Google Scholar 

  31. Yuan Z, Ye Y, Gao F, et al. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release. International Journal of Pharmaceutics, 2013, 446(1–2): 191–198

    Article  Google Scholar 

  32. Prabaharan M, Gong S. Novel thiolated carboxymethyl chitosan-g-β-cyclodextrin as mucoadhesive hydrophobic drug delivery carriers. Carbohydrate Polymers, 2008, 73(1): 117–125

    Article  Google Scholar 

  33. Ito T, Iida-Tanaka N, Niidome T, et al. Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation. Journal of Controlled Release, 2006, 112(3): 382–388

    Article  Google Scholar 

  34. Deng X, Cao M, Zhang J, et al. Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer. Biomaterials, 2014, 35(14): 4333–4344

    Article  Google Scholar 

  35. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Experimental and Molecular Pathology, 2009, 86(3): 215–223

    Article  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Samir Acherar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mihoub, A.B., Saidat, B., Bal, Y. et al. 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. Front. Mater. Sci. 12, 83–94 (2018). https://doi.org/10.1007/s11706-018-0407-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11706-018-0407-2

Keywords

Navigation