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Preparation And Evaluation Of 5-FU/PLGA/Gene Nanoparticles

Yun Xiang Hu, Jin Chang, Yi Guo, Xu Bo Yuan, Chun Sheng Kang, Peiyu Pu

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In this study, we constructed a novel drug delivery system for realizing the combination of gene therapy and chemotherapy by co-loading 5-FU and antisense EGFR (epidermal growth factor receptor) plasmids in biodegradable PLGA/O-CMC (O-carboxmethyl-chitosan) nanoparticles. This novel kind of nanoparticle was characterized by dynamic light scattering for size, size distribution and zeta potential, and scanning electron microscopy (SEM) and transmission electronic microscopy (TEM) for morphological properties and structures. Drug encapsulation efficiency and drug release kinetics under in vitro conditions were also measured. At the same time, the MTT assay, the TUNEL technique and immunohistochemical staining were used to investigate the antitumor activity of these multi-functional nanoparticles on human glioma cells. It was concluded that the 5-FU and plasmid encapsulation efficiencies were as high as 94.5% and 95.7%, and the 5-FU release activity from nanoparticles could be sustained for as long as three weeks. Both the MTT assay and the TUNEL method illustrated that these multi-functional nanoparticles had cytotoxicities as high as 93.5% and could induce apoptosis in most glioma cells. Immunohistochemical staining proved that plasmids on the surface of nanoparticles could transfect gliomas cells, verified by a decline in the expression level of EGFR protein by the glioma cells. Therefore, this novel delivery system for drugs and genes provides another therapeutic pathway for cancer and needs further research.