Preparation And Anti-carcinoma Effect Of Chitosan-Polyaspartic Acid-5Fluorouracil Nanoparticles On Tumor Growth Of The Implanted Gastric Cancer In Nude Mice

Objective:In order to increase the oral administration effect of 5-Fluorouracil (5-FU),we prepare Chitosan-Polyaspartic acid-5Fluorouracil(CTS-Pasp-SFU) Nanoparticles and investigate its anti-carcinoma effect and toxicity.Methods CTS-Pasp-SFU nanoparticles were synthesized by ion gelatification. Dynamic light scattering(DLS) was used to measure the hydrodynamic diameter and size distribution.The morphology and dried TEM-assessed size measurement of the CTS-Pasp-SFU nanoparticles were examined under transmission electron microscopy (TEM).The amount of free 5-FU in the supernatant was measured by HPLC.The 5-FU encapsulation efficiency(EE) and the 5-FU loading capacity(LC) of the nanoparticles were calculated.Male BABL/c nude mice were injected with SGC-7901 gastric carcinoma cell line mass subcutaneously near nape to establish human gastric carcinoma model.Then they were randomly allocated into 4 groups: chitosan-polyaspartic acid -Sfluorouracil(CTS-Pasp-5FU)(containing 5-FU 1.25mg/kg),5-Fu(1.25mg/kg),chitosan-polyaspartic acid group and normal saline group.The tumor volume and weight of nude mice were measurded every other day. The inhibition rate of tumor growth(IR) was calculated based on the results.The tumor was weighed when the experiment was over and the tumor inhibition rates(TIR) were calculated.The WBC,TB,Cr,ALT was decteded and the assay of colony forming unit-granulocyte and macrophage(CFU-GM) was performed after the experiment.The architecture change of cells and tissues was observed and the bax and bcl-2 gene was detected.Results Stable CTS-Pasp-SFU nanoparticles were prepared.The diameter of the particles were about 190nm and 5-FU disperses within the nanoparticles.The drug content of CTS-Pasp-SFU was 40.2%and the enclosed quotiety was 30.9%in this research.At the end of the experiment,6 of 8 nude mice survived in the 5-FU group and no mouse died in the other three groups.The inhibition rate of tumor growth(IR) of the 5-FU and CTS-Pasp-SFU groups was significantly higher than NS group (58.69%,P＜0.05;70.82%,P＜0.001).There was no difference in the IR between CTS-Pasp and NS groups(5.58%,P＞0.05).Tumor inhibition rate(TIR) of CTS-Pasp-5FU and 5FU groups was significantly higher than NS group(72.79%and 65.3%;P＜0.05).There was a significant decrease in the number of CFU-GM formation and increase in total bilirubin,ALT in 5-FU group,but no changes in those of the other three groups.And there were no significant changes in white blood cells and creatinine among four groups.Pathological section of liver and nephridial tissue shows that the damage of 5-FU group is severe than that of CTS-Pasp-5FU group. 5-FU group and CTS-Pasp-5FU group can both down regulate the bcl-2 expression and up-regulate the bax expression to different extent,and the accommodate effect of CTS-Pasp-5FU is obviously than 5-FU group.Conclusions CTS-Pasp-5FU nanoparticles can successfully synthesized by ion gelatification.Compared with 5-Fu,CTS-Pasp-5FU nanoparticles can raise the anti-carcinoma effect and degrade the hepatoxicity and bone marrow depression.It is a safe,effective and new anti-carcinoma preparation,with favourable prospect in clinical application.