Experimental Study On The Growth Inhibition Effection Of 5-fluorouracil Loaded Chitosan Sustained-release Micro-spheres To The Gastric Cancer Cells Of Peritoneal Implanta-tion In Nude Mice

Objective: Investigation the growth inhibitory effection of 5- fluorouracil loaded chi- tosan sustained-release microspheres to the gastric cancer cells of peritoneal implantation in nude mice.Methods: The microspheres were prepared using emulsified-chemical cross-linking method : the water phase which consisted of 5-fluorouracil dissolved in 5% acetic acid and chitosan added after 5-fluorouracil was dissolved was droppded into the oil phase of paraffin oil , emulsification by ultrasound and using 25% glutaraldehyde to cross-link, then obtained the microspheres by vacuum drying. The same method, only without 5 - fluorouracil obtained blank microspheres. Observed basic characteristics of the microspheres and studied the drug encapsulation efficiency and the Drug load- ing. Weighed the microspheres 142 mg (include 5 - fluorouracil 50mg)and 5 - fluorouracil powder 50mg , placed them in dialysis bags, observed the role of drug release in vitro by determining con- centration and cumulative release hourly in 24h,then Once a day and a total of seven days . Establish the model of peritoneal implantation of gastric cancer cells in nude mice, calculated according to body surface area of 5 - fluorouracil dosage, con- version out of the dosage of 5- fluorouracil loaded chitosan sustained-release micro- spheres. All 32 nude mice divided into four groups randomly: A group(5- fluorouracil loaded chito- san sustained-release microspheres group),B group(blank microspheres group),C group(5- fluorouracil group)and D group(NS group), the nude mice were in- jected into the abdominal cavity 5- fluorouracil loaded chitosan sustained-release microspheres,blank microspheres,5- fluorouracil,NS by groups. Studied the changes of the every mouse body weight and abdominal circumference,the number of peritoneal metastatic noduli,the rate of gastric cancer cells apoptosis,survival of the nude mouse and the drug toxicity.Results: The average particle size of the microspheres was (185.5±15.0)nm, drug-loading rate was (35.2±0.8)% and encapsulation efficiency was ( 49.3±2.1)%. The microspheres release experiments in vitro showed that it released 5-fluorouracil 21.4±3.6μg/ml in the first hour,123.2±3.6μg/ml on the first day and 4.5±0.6/ml on the seventh day by releasing slowly. In the nude mice of A group ,The survival rate was more than the nude mice of B group (P< 0.05),the nude mice of C group(P< 0.05)and the nude mice of D group(P< 0.01), the number of peritoneal metastatic noduli in the nude mice of A group was less than the nude mice of other group(P<0.05), the rate of gastric cancer cells apoptosis in the nude mice of A group was more than the nude mice of B group (P< 0.05),the nude mice of C group(P<0.05)and the nude mice of D group(P< 0.01) when the difference in the number of WBC,ALT,BUN,TBI of Vein blood in the nude mice compared with other groups showed no statistical significance (P> 0.05).Conclusions: The 5- fluorouracil loaded chitosan sustained- release microspheres have uniform distribution,good drug encapsulation efficiency and drug release. The microspheres show perfect growth inhibition effect to gastric cancer cells of peritoneal implantation in nude mice and can improve the prognosis of the mice.