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Chitosan-Based Polyelectrolyte Complexes for Doxorubicin and Zoledronic Acid Combined Therapy to Overcome Multidrug Resistance

1
Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy
2
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, L. De Crecchio 7, 80138 Naples, Italy
3
UOSD SAFU, IRCCS Regina Elena National Cancer Institute, E. Chianesi 53, 00144 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2018, 10(4), 180; https://doi.org/10.3390/pharmaceutics10040180
Received: 4 September 2018 / Revised: 2 October 2018 / Accepted: 5 October 2018 / Published: 9 October 2018
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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Abstract

This study aimed to develop nanovectors co-encapsulating doxorubicin (Doxo) and zoledronic acid (Zol) for a combined therapy against Doxo-resistant tumors. Chitosan (CHI)-based polyelectrolyte complexes (PECs) prepared by ionotropic gelation technique were proposed. The influence of some experimental parameters was evaluated in order to optimize the PECs in terms of size and polydispersity index (PI). PEC stability was studied by monitoring size and zeta potential over time. In vitro studies were carried out on wild-type and Doxo-resistant cell lines, to assess both the synergism between Doxo and Zol, as well as the restoring of Doxo sensitivity. Polymer concentration, incubation time, and use of a surfactant were found to be crucial to achieving small size and monodisperse PECs. Doxo and Zol, only when encapsulated in PECs, showed a synergistic antiproliferative effect in all the tested cell lines. Importantly, the incubation of Doxo-resistant cell lines with Doxo/Zol co-encapsulating PECs resulted in the restoration of Doxo sensitivity. View Full-Text
Keywords: chitosan; polyelectrolyte complexes; doxorubicin; zoledronic acid; multidrug resistance chitosan; polyelectrolyte complexes; doxorubicin; zoledronic acid; multidrug resistance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Giarra, S.; Zappavigna, S.; Campani, V.; Abate, M.; Cossu, A.M.; Leonetti, C.; Porru, M.; Mayol, L.; Caraglia, M.; De Rosa, G. Chitosan-Based Polyelectrolyte Complexes for Doxorubicin and Zoledronic Acid Combined Therapy to Overcome Multidrug Resistance. Pharmaceutics 2018, 10, 180.

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