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Citric acid-γ-cyclodextrin crosslinked oligomers as carriers for doxorubicin delivery

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Abstract

Two citric acid crosslinked γ-cyclodextrin oligomers (pγ-CyD) with a MW of 21-33 kDa and 10-15 γ-CyD units per molecule were prepared by following green chemistry methods and were fully characterized. The non-covalent association of doxorubicin (DOX) with these macromolecules was investigated in neutral aqueous medium by means of circular dichroism (CD), UV-vis absorption and fluorescence. Global analysis of multiwavelength spectroscopic CD and fluorescence titration data, taking into account the DOX monomer-dimer equilibrium, evidenced the formation of 1?:?1 and 1?:?2 pγ-CyD unit-DOX complexes. The binding constants are 1-2 orders of magnitude higher than those obtained for γ-CyD and depend on the characteristics of the oligomer batch used. The concentration profiles of the species in solution evidence the progressive monomerization of DOX with increasing oligomer concentration. Confocal fluorescence imaging and spectral imaging showed a similar drug distribution within the MCF-7 cell line incubated with either DOX complexed to pγ-CyD or free DOX. In both cases DOX is taken up into the cell nucleus without any degradation.

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Authors and Affiliations

  1. Institute for Organic Synthesis and Photoreactivity, CNR, via P. Gobetti 101, 40129, Bologna, Italy

    Resmi Anand, Ilse Manet, Francesco Manoli & Sandra Monti

  2. CycloLab, Cyclodextrin R&D Ltd., H1097, Budapest, Hungary

    Milo Malanga, Kata Tuza & Eva Fenyvesi

  3. Departamento de Química y Física, Universidad de Almería, Carretera de Sacramento s/n, 04120, Almería, Spain

    Ahmet Aykaç & Antonio Vargas-Berenguel

  4. Ecole Polytechnique Universitaire Lyon, 1, UMR CNRS 5223/IMP, Villeurbanne Cedex, France

    C. Ladavière

  5. UMR 8612 CNRS Université Paris-Sud, Châtenay-Malabry, France

    Ruxandra Gref

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  1. Resmi Anand
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Anand, R., Malanga, M., Manet, I. et al. Citric acid-γ-cyclodextrin crosslinked oligomers as carriers for doxorubicin delivery. Photochem Photobiol Sci 12, 1841–1854 (2013). https://doi.org/10.1039/c3pp50169h

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