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World J Gastroenterol. Jun 14, 2008; 14(22): 3554-3562
Published online Jun 14, 2008. doi: 10.3748/wjg.14.3554
Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice
Dan-Ying Zhang, Xi-Zhong Shen, Ji-Yao Wang, Ling Dong, Yong-Li Zheng, Li-Li Wu
Dan-Ying Zhang, Xi-Zhong Shen, Ji-Yao Wang, Ling Dong, Li-Li Wu, Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
Yong-Li Zheng, Department of Macromolecular Science, Key Laboratory of Molecular Engineering of Polymers of Chinese Ministry of Education, Fudan University, 220 Handan Road, Shanghai 200433, China
Author contributions: Zhang DY and Dong L contributed equally to this work; Zhang DY, Shen XZ and Dong L designed the research; Zhang DY, Dong L and Zheng YL performed the research; Zheng YL provided new reagents/analytic tools; Zhang DY, Dong L and Wu LL analyzed data; and Zhang DY and Dong L wrote the paper.
Correspondence to: Ling Dong, Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China. dltalk@tom.com
Telephone: +86-21-54231990
Received: August 23, 2007
Revised: September 19, 2007
Accepted: September 26, 2007
Published online: June 14, 2008
Abstract

AIM: To prepare chitosan-polyaspartic acid-5-fluorouracil (CTS-Pasp-5Fu) nanoparticles and investigate its anti-carcinoma effect and toxicity.

METHODS: CTS-Pasp-5Fu nanoparticles were synthesized by ionic gelatification. Male BABL/c nude mice were injected with SGC-7901 gastric carcinoma cell line mass to establish a human gastric carcinoma model. They were randomly allocated into 4 groups: CTS-Pasp-5Fu (containing 5-Fu 1.25 mg/kg), 5-Fu (1.25 mg/kg), CTS-Pasp and normal saline groups. Tumor weight was measured and assay of colony forming unit-granulocyte and macrophage (CFU-GM) was performed. The structural change of cells and tissues was observed and the Bax and Bcl-2 genes were detected.

RESULTS: Compared with normal saline, the inhibition rates of tumor growth for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.58%, 58.69% and 70.82%, respectively. The tumor inhibition rates for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.09%, 65.3% and 72.79%, respectively. There was a significant decrease in the number of CFU-GM formation and increase of total bilirubin, and alanine aminotransferase in the 5-Fu group, but no change in those of the other three groups. There was no change in white blood cell count and creatinine among the four groups. Pathological section of liver and nephridial tissues showed that the damage in the 5-Fu group was more severe than that in the CTS-Pasp-5Fu group. 5-Fu and CTS-Pasp-5Fu groups could both down-regulate the Bcl-2 expression and up-regulate the Bax expression to different extent, and the accommodate effect of CTS-Pasp-5Fu was more obvious than 5-Fu.

CONCLUSION: The tumor inhibition rate of CTS-Pasp-5Fu nanoparticles is much higher than that of 5-Fu alone.

Keywords: 5-Fluorouracil; Chitosan; Polyaspartic acid; Nanoparticles; Gastric carcinoma