Title:Preparation of Modified Chitosan-based Nanoparticles for Efficient
Delivery of Doxorubicin and/or Cisplatin to Breast Cancer Cells
Volume: 22
Issue: 2
Author(s): Sina M. Matalqah*, Khalid Aiedeh, Nizar M. Mhaidat, Karem H. Alzoubi and Belal A. AL-Husein
Affiliation:
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
Keywords:
pH-responsive nanoparticles, modified chitosan, cross-linked nanoparticles, controlled drug release, cisplatin, breast cancer cells.
Abstract:
Purpose: The aim is to develop a novel pH-responsive modified chitosan-based nanoparticles
system for active loading of doxorubicin (DOX) and triggered intracellular release.
Methods: Nanoparticles were formed in an aqueous medium via ionic interaction between negatively
charged chitosan derivative and positively charged DOX at neutral pH and then transformed in situ
into cisplatin (CIS) cross-linked nanoparticles through cross-linking the formed micelles via chelation
interaction between the negatively charged polymeric carrier and cisplatin. Nanoparticles were characterized
in terms of particle size and zeta potential using DLS and TEM. Drug loading efficiency and
encapsulation efficiency were determined based on the physio-chemical proprieties of the polymer and
the amount of the cross-linking agent. In vitro release studies were performed using the dialysis method
at different pHs. Finally, the cytotoxic effects of these nanoparticles were performed against the
MCF-7 BrCA cell line under different pHs.
Results: The average particle size of polymer alone and DOX nanoparticles was 277.401 ± 13.50 nm
and 290.20 ± 17.43 nm, respectively. The zeta potential was -14.6 ± 1.02 mV and -13.2 ± 0.55 mV,
respectively, with a low polydispersity index. Drug loading and encapsulation deficiencies were determined,
dependent on the amount of the cross-linking agent. In vitro release studies showed that the
release of DOX from these nanoparticles was pH-dependent. Moreover, results showed that the cytotoxicity
magnitude of DOX-loaded nanoparticles against MCF-7 BrCA cells was higher compared
with free DOX.
Conclusion: These novel pH-sensitive nanoparticles proved to be a promising Nano-drug delivery for
tumor-targeted delivery of DOX.
