| Summary: | 博士 === 國立臺灣科技大學 === 應用科技研究所 === 107 === Hepatocellular carcinoma(HCC) is the fourth leading cause of cancer-related death in the world and the second leading cause in Taiwan. For unresectable HCC, transcatheter arterial chemoembolization(TACE) is one of the current standard therapy, but it may promote a proangiogenic response at the tumor site and induce inflammation in the body.
In this study, new types of spherical, biodegradable, therapeutically synergistic, and drug-loadable delivery vehicles were developed to improve the efficacy of hepatic tumor embolization and hepatic artery infusion chemotherapy. A series of novel polysaccharide based microparticles(MPs) including doxorubicin(DOX)-chondroitin sulfate(ChS)/chitosan(CS), DOX-superparamagnetic iron oxide(SPIO)-ChS/CS and DOX-SPIO/N-palmitoyl chitosan(NPCS) MPs were prepared for hepatic cancer treatment. The morphology and size of the MPs were investigated by transmission and scanning electron microscopy. The MPs had the diameters from 185±87nm to 1.43±0.54 μm. The success of encapsulating SPIO was verified by transmission electron microscopy(TEM), X-ray photoelectron spectroscopy(XPS) and nuclear magnetic resonance T2 imaging(NMRI). In the drug release profile, the MPs showed slow releasing effect, and DOX-SPIO/NPCS MPs was accelerated in acidic environment(pH 6.5) compared with that in a basic environment. MPs present heating effects under external magnetic field. Results of cytotoxicity assay(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) exhibited that MPs had better antitumor ability than free-form of DOX. According to the results of an animal study, the DOX-SPIO-ChS/CS MPs demonstrated stronger anti-tumor effect than free-form of DOX when it was administered to xenograft nude mice of HepG2/Huh6-bearing mice model in vivo. Thus, all these results suggested a considerable potential of MPs as a drug delivery system for hepatic cancer therapy.
|
|---|
