Preparation And Evaluation In Vitro Of PLGA Loaded 5-FU Wafer And Study Of PLA Loaded 5-FU Microspheres In Vivo Anti-Gastric Tumor

5-fluorouracil(5-FU) loaded Microspheres(MS) were prepared by improved double emulsion (W/O/W) method using Poly(D,L-lactide-co-glycolide) (PLGA) as carrier, F-68 and PEG-2000 used as emulsifier. The 5-FU-MS were characterized for drug content, loading efficiency, yield, release behavior. Prepared MS was compressed to wafer by compression moulder. The influence factors for wafer release in vitro including release medium, average molecular weight, the ratio of LA/GA, and different protection methods were discussed. The MS prepared by improved W/O/W method were spherical in shape, had smooth external morphology. The best conditions of the preparation were that the concentration of 5-FU,F-68,PEG-2000 was 5%,0.3% and 3% respectively. The volume ratio of ethyl acetate/acetone was 1:1; The release behavior of 5-FU from 5-FU-PLGA wafer was characterized, (1) The release behavior of 5-FU-PLGA wafer in PBS (pH=7.4) was better than in PBS(pH=4.0) and in PBS(pH=9.18). (2) The higher the ratio of LA/GA, the faster release speed. (3) The release rate of wafer which was prepared by low average molecular weight PLGA is faster than high average molecular weight PLGA. (4) The burst release of wafer protected by blank MS was restrained, however, no obvious restrain effect was observed for wafer protected by PVA for its quickly falling off.The therapeutic efficacy of these MS was also examined. The life span of SCID nude mice and tumor volume restrain ratio were selected as evaluation indexes. (1) The life span of free 5-FU group was 14.3days, prolonged 19.16% compared with controlled group.(2)The median survival time for the 1μm and 5μm microsphere-treated animals were 40.6 and 62.3 days, respectively, prolonged 2.38 times and 4.19 times, respectively. Because MS-treated group has obvious controlled release effect, the median survival time of MS-treated group is longer than free drug group. (3)The tumor volume restrain ratio of free 5-FU group, 1μm and 5μm MS-treated group were 86.75%, 45.27%, 35.07%, though free 5-FU group was higher than MS-treated groups. The median survival time of 1μm and 5μm microsphere-treated group was longer than free 5-FU group because of its toxicity. These results strongly implicate that the 5-FU- PLA MS could offer a safer yet more effective clinical avenue in treating gastrointestinal tumors.