Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

摘要

Background: Although conventional chemotherapy is the most common method for cancer treatment,it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given tobody systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drugdelivery has been developed to overcome these drawbacks.Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent andD-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells.For this purpose, magnetic nanoparticles (MNPs) were synthesized and coated with oleic acid (OA). Coatednanoparticles were encapsulated in poly (lactic-co-glycolic acid (PLGA) and TPGS polymers and loaded withDox. The nanoparticles (NPs) were characterized by fourier transform infrared (FTIR) spectroscopy, zetapotentialanalysis, dynamic light scattering (DLS) analysis, thermal gravimetric analysis (TGA) and scanningelectron microscope (SEM) analysis.Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drugtargeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA andFTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7)and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicitysignificantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF-7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs.Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapyand could be used for breast cancer treatment after in vivo tests.