Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery

Abstract

Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field. Among various materials, chitosan has a great importance as a pH sensitive, natural, biodegradable, biocompatible and bioadhesive polymer. The aim of this study was to obtain an effective targeted delivery system for Doxorubicin, using chitosan coated MNPs. Different sized CS MNPs were produced by in situ synthesis method. The anti-cancer agent Doxorubicin was loaded onto CS MNPs which were characterized previously. Doxorubicin loading was confirmed by FTIR. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Our results showed that the CS MNPs have pH responsive release characteristics. The cellular internalization of Doxorubicin loaded CS MNPs were visualized by fluorescent microscopy. Doxorubicin loaded CS MNPs are efficiently taken up by MCF-7 (MCF-7/S) and Doxorubicin resistant MCF-7 (MCF-7/1 mu M) breast cancer cells, which increases the efficacy of drug and also maintains overcoming the resistance of Doxorubicin in MCF-7/Dox cells. Consequently, CS MNPs synthesized at various sizes can be effectively used for the pH dependent release of Doxorubicin in cancer cells. Results of this study can provide new insights in the development of pH responsive targeted drug delivery systems to overcome the side effects of conventional chemotherapy. (C) 2014 Elsevier B.V. All rights reserved.