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

  • Biomaterials Synthesis and Characterization
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Abstract

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.

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Pharmacy, University of Pisa, via Bonanno 33, 56126, Pisa, Italy

    Anna Maria Piras, Ylenia Zambito, Susi Burgalassi, Daniela Monti, Silvia Tampucci, Eleonora Terreni, Angela Fabiano & Patrizia Chetoni

  2. Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi 13, 56124, Pisa, Italy

    Federica Balzano & Gloria Uccello-Barretta

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  1. Anna Maria Piras
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Correspondence to Anna Maria Piras.

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Piras, A.M., Zambito, Y., Burgalassi, S. et al. A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone. J Mater Sci: Mater Med 29, 42 (2018). https://doi.org/10.1007/s10856-018-6048-2

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