Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice.
OBJECTIVE
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.


CONCLUSIONS
The tumor inhibition rate of CTS-Pasp-5Fu nanoparticles is much higher than that of 5-Fu alone.
Zhang
Dan-Ying
DY
Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Shen
Xi-Zhong
XZ
Wang
Ji-Yao
JY
Dong
Ling
L
Zheng
Yong-Li
YL
Wu
Li-Li
LL
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C017645:polyaspartate; D048271:Chitosan; D005472:Fluorouracil