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

1 Citation (Scopus)

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

Fingerprint

zoledronic acid
Chitosan
Multiple Drug Resistance
Doxorubicin
Therapeutics
Cell Line
Polyelectrolytes

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Chitosan-based polyelectrolyte complexes for doxorubicin and zoledronic acid combined therapy to overcome multidrug resistance. / Giarra, Simona; Zappavigna, Silvia; Campani, Virginia; Abate, Marianna; Cossu, Alessia Maria; Leonetti, Carlo; Porru, Manuela; Mayol, Laura; Caraglia, Michele; De Rosa, Giuseppe.

In: Pharmaceutics, Vol. 10, No. 4, 01.12.2018, p. 180.

Research output: Contribution to journalArticle

Giarra, Simona ; Zappavigna, Silvia ; Campani, Virginia ; Abate, Marianna ; Cossu, Alessia Maria ; Leonetti, Carlo ; Porru, Manuela ; Mayol, Laura ; Caraglia, Michele ; De Rosa, Giuseppe. / Chitosan-based polyelectrolyte complexes for doxorubicin and zoledronic acid combined therapy to overcome multidrug resistance. In: Pharmaceutics. 2018 ; Vol. 10, No. 4. pp. 180.
@article{2465e94dbb95473bba8c37dd4e8c02dc,
title = "Chitosan-based polyelectrolyte complexes for doxorubicin and zoledronic acid combined therapy to overcome multidrug resistance",
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.",
keywords = "Chitosan, Doxorubicin, Multidrug resistance, Polyelectrolyte complexes, Zoledronic acid",
author = "Simona Giarra and Silvia Zappavigna and Virginia Campani and Marianna Abate and Cossu, {Alessia Maria} and Carlo Leonetti and Manuela Porru and Laura Mayol and Michele Caraglia and {De Rosa}, Giuseppe",
year = "2018",
month = "12",
day = "1",
doi = "10.3390/pharmaceutics10040180",
language = "English",
volume = "10",
pages = "180",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

TY - JOUR

T1 - Chitosan-based polyelectrolyte complexes for doxorubicin and zoledronic acid combined therapy to overcome multidrug resistance

AU - Giarra, Simona

AU - Zappavigna, Silvia

AU - Campani, Virginia

AU - Abate, Marianna

AU - Cossu, Alessia Maria

AU - Leonetti, Carlo

AU - Porru, Manuela

AU - Mayol, Laura

AU - Caraglia, Michele

AU - De Rosa, Giuseppe

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Chitosan

KW - Doxorubicin

KW - Multidrug resistance

KW - Polyelectrolyte complexes

KW - Zoledronic acid

UR - http://www.scopus.com/inward/record.url?scp=85056133846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056133846&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics10040180

DO - 10.3390/pharmaceutics10040180

M3 - Article

AN - SCOPUS:85056133846

VL - 10

SP - 180

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 4

ER -