Preparation, characterisation and in vitro cytotoxicity studies of chelerythrine-loaded magnetic Fe₃O₄@O-carboxymethylchitosan nanoparticles

摘要

In this work, a novel, active tumour-targeting system (Fe_(3)O_(4)@OCMCS-CHE) was designed by surface-modifying superparamagnetic iron oxide nanoparticles (Fe_(3)O_(4)) with O-carboxymethylchitosan (OCMCS) to improve their biocompatibility and ability to target specific tumour cells. The chelerythrine (CHE) was used as the model of anti-tumour drug in this system. The optimised formulation was characterised and confirmed by scanning electron microscopy (SEM), transmission electron microscope (TEM), vibrating sample magnetometer (VSM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), in vitro drug release and so on. It was found that the synthesised nanoparticles were spherical in shape with an average size of 60 nm, the drug loading content and entrapment efficiency were 8.32 ± 0.25% (w/w) and 90.65 ± 0.46% (w/w), respectively, and the saturated magnetisation reached 27.06 emu/g. The in vitro drug-release behaviour from nanoparticles displayed a biphasic drug-release pattern with initial burst release and consequently sustained release. Also, the effect of magnetic targeted nanoparticles on the proliferation of human hepatoma cell line (HepG2) in vitro was investigated. The results from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hochest assays suggested that the Fe_(3)O_(4)@OCMCS-CHE nanoparticles could effectively inhibit the proliferation of HepG2 cells, which displayed time-dependent and concentration-dependent manner. All these results indicated that the multifunctional Fe_(3)O_(4)@OCMCS nanoparticles possess a high drug loading efficiency, have low cytotoxicity, and are promising candidates for targeted drug delivery.