Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Chitosan coated magnetic iron-oxide nanoparticles (CSMNPs) can be targeted to the tumor site under magnetic field and maintain pH dependent drug release. Among various materials, chitosan has a great importance as a pH sensitive, natural, biodegradable, biocompatible and bio-adhesive polymer. CSMNPs were in-situ synthesized at different sizes by ionic crosslinking method. XRD and XPS analyses proved that synthesized iron-oxide was magnetite (Fe3O4). Chitosan coating on magnetite was detected by FTIR and chitosan amount was 23% in TGA. CSMNPs were found super-paramagnetic by VSM. Average core size was 8 nm in TEM and hydrodynamic diameter was 103 nm in DLS. The anti-cancer drug doxorubicin was loaded on CSMNPs (Dox-CSMNPs) and loading was confirmed by FTIR. 30% of doxorubicin was released at pH 4.2 in first 7 hours. Dox-CSMNPs are efficiently taken up by MCF-7 and 1 �¼M Doxorubicin resistant MCF-7 (MCF-7/Dox) breast cancer cells. CSMNPs increase the efficacy of Doxorubicin by increasing the cellular uptake of drug and overcome the resistance of Doxorubicin in resistant cells. When these drugs are loaded on CSMNPs, the anti-proliferative efficiencies of drugs increases and resistance to these drugs is eliminated. In vitro cytotoxicity analyses also revealed that IC50 values of drug 13 fold decreases when loaded on CSMNPs. Pro-apoptotic Puma and Noxa genes were up-regulated while anti-apoptotic Bcl-2, Survivin and cIAP-2 genes were down-regulated in Dox-CSMNP treated cells. This study provides new insights to the development of pH responsive magnetic targeted drug delivery systems to overcome the side effects and resistance problem of conventional chemotherapy.

Biography

Email: gozdeunsoy@hotmail.com