Chitosan-based polyelectrolyte complexes for doxorubicin and zoledronic acid combined therapy to overcome multidrug resistance

Simona Giarra, Silvia Zappavigna, Virginia Campani, Marianna Abate, Alessia Maria Cossu, Carlo Leonetti, Manuela Porru, Laura Mayol, Michele Caraglia, Giuseppe De Rosa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)180
JournalPharmaceutics
Volume10
Issue number4
DOIs
Publication statusPublished - Dec 1 2018

Keywords

  • Chitosan
  • Doxorubicin
  • Multidrug resistance
  • Polyelectrolyte complexes
  • Zoledronic acid

ASJC Scopus subject areas

  • Pharmaceutical Science

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