Preparation And Cell Toxicity Of 5'-Palmito Yl-5-Fluo Rouridine Liposome

5-fluorouridine (5-FUR), the crude drug of 5-fluoro-2-deoxyuridine (FUdR), has antitumor activity above that of FUdR in vitro and in vivo. However, 5-FUR is not used in clinical, as it has no sensitive and strong side effects such as leukopenia, thrombopenia, and gastrointestinal toxicity.Liposomes have attracted considerable interest, because of their favorable characteristics as carriers for toxic compounds. The goal of using liposomes as a drug delivery system is to enhance the therapeutic index of the drugs,induce the dose and side effect of the drugs.Resently,to increase delivery efficiency,liposomes have been designed with target agents.such as pH angent,antibody and so on. However, 5-FUR is a water soluble drug, has a poor entrapment efficiency. For this reason, 5-FUR has usually been incorporated into the lipid vesicle as lipophilic prodrug: 5′-palmitoyl- 5-fluorouridine (5-FURP) .We had applied a reverse-phase evaporation vesicles(REV) to prepare 5-FURP liposome. Through orthogonal experimental design, one optimum recipes of 5-FURP liposome was founded that it showed Drug/EPC 1:10, EPC/Ch 3:1, sonication time 5min. Under the optimal formulation, 5-FURP was encapsulated 94.35%.A method was developed for the determination of 5-FURP concentration in liposomes and entrapment efficiency by UV, it was proved that this method was accurate, sensitive. The small unilamellar vesicle liposomes were observed by inverted phase contrast microscope. The stability of 5-FURP liposome was valuated with the entrapment efficiency and the change of EPC value in 4, 25℃for 1 month. The results showed that the 5-FURP liposome stored in 4℃would keep stabilitable.The cytotoxic activity of the liposomes encapsulated with 5-FURP was tested on human breast cancer of MCF-7 cell line,human nasopharyngeal carcinoma of CNE-1 cell line,human nasopharyngeal carcinoma of HEP-2 cell line.The result of the lipophilic prodrug liposome was higher than that of the free drug.The IC50 of 5-FURP liposome was higher(5 times , 3.4times, 2.6times) for the MCF-7, CNE-1 ,H EP-2 than that of the free 5-FUR.And was demonstrated development value of 5-FUR.