A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

  • Anna Maria PirasEmail author
  • Ylenia Zambito
  • Susi Burgalassi
  • Daniela Monti
  • Silvia Tampucci
  • Eleonora Terreni
  • Angela Fabiano
  • Federica Balzano
  • Gloria Uccello-Barretta
  • Patrizia Chetoni
Biomaterials Synthesis and Characterization Original Research
Part of the following topical collections:
  1. Biomaterials Synthesis and Characterization


The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.



We gratefully acknowledge the financial support from P.R.A. 2017 by the University of Pisa.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10856_2018_6048_MOESM1_ESM.pdf (545 kb)
Supplementary Material


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Anna Maria Piras
    • 1
    Email author
  • Ylenia Zambito
    • 1
  • Susi Burgalassi
    • 1
  • Daniela Monti
    • 1
  • Silvia Tampucci
    • 1
  • Eleonora Terreni
    • 1
  • Angela Fabiano
    • 1
  • Federica Balzano
    • 2
  • Gloria Uccello-Barretta
    • 2
  • Patrizia Chetoni
    • 1
  1. 1.Department of PharmacyUniversity of PisaPisaItaly
  2. 2.Department of Chemistry and Industrial ChemistryUniversity of PisaPisaItaly

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