Synthesis And Characterization Of DOX-Dextran Composite Magnetic Particle And Its Application As A Drug Carrier In Vitro

Magnetic targeted drug delievery system (MTDDS) is a promising aspect of targeted durg delievery system (TDDS). Using the magnetic field the drug-loaded magnetic particle can be located to the targeted tissue, this method can cure the cancer with little side effects to patients. Dextan-coated magnetic particle is an excellent drug carrier for mgnetic targeted drug delievery system because of its non-toxicity and well biocompatible ablity.In this study the DOX-dextran composite magnetic particles were synthesized by two-steps: redispertion and cross linking. The obtained dextran composite magnetic particle showed superparamagnetic behavior. Its application as a magnetic drug carrier for magnetic targeted drug delievery system and cytotoxicity in vitro were also investigated. The details of the experiments are described as follows:1) The synthesis and characterization of dextran-coated magnetic particle: comparing the chemical coprecipitation method with ultrasonication method, the ultrasonication method was choosed as the suitable method to synthsize the dextran-coated magnetic particle. The molecular weight of dextran, the time of ultrasonication and the concentration of NaOH were optimized during the synthesis of the dextran-coated magnetic particle by ultrasonication. The saturated magnetization of dxtran-coated magnetic particle was 6.78 emu/g and had an average size at 130 nm.2) The synthesis and characterization of cross-linked dextran composite magnetic particle: Using the Epichlorohydrin (ECH) as the cross linking reagent, the dextran composite magnetic particle was synthesized. The volume of cross-linked reagent and the concentration of NaOH were optimized during synthesis of cross-linked dextran-coated magnetic particle. The saturated magnetization of the obtained composite magnetic particle was 48.6 emu/g, the size distribution of the obtained composite magnetic particles were 1μm -3μm and had 58.9% Fe in weight. 3) The synthesis of doxorubicin (DOX)-dextran composite magnetic particles: the DOX-dextran composite magnetic particles were synthesized by loading DOX on the cross-linked dextran composite magnetic particle. The DOX loaded on the dextran composited magnetic particle was saturated after stirring for 72 h at room temperature with capacity of 78μg/mg. The cumulative percentage of released DOX in 1×PBS buffer (pH = 7.4) at 2 d, 3 d and 7 d were 63%, 66.5% and 69.4%, respectively. The results showed that the cross-linked dextran-coated magnetic particle had a sustained drug release ability.4) The cell experiments with dextran composite magnetic particle and DOX-dextran composite magnetic particle in vitro: the cytotoxicity experiment with dextran composite magnetic particle and DOX-dextran composite magnetic particle, which were carried out by the method of MTT assay with HepG2 cell line. The result showed the dextran composite magnetic particle had no obvious cytotoxicity to HepG2 cell line below the concentration of 50μg/mL. The DOX-dextran composite magnetic particle exhibited cell inhibition to the HepG2 cell line and had IC50 of 186μg/mL, besides it showed a sustained drug release ability of DOX in the cell culture fluid.