Pharmacokinetics of chitosan-polyaspartic acid-5-fluorouracil nanoparticles in mice / 中国组织工程研究

ABSTRACT

BACKGROUND: 5-fluorouracil (5-Fu) is universally used as an antineoplastic agent in gastrointestinal cancer, but the side effect of it confined further clinical application. OBJECTIVE: To determinate mice plasma concentration curves for 5-Fu and its chitosan (CS)-polyaspartic acid (Pasp) nanoparticles, and to investigate their primary pharrnacokinetics. DESIGN, TIME AND SETTING: Randomization control animal trials were performed in the Department of Gastroenterology, Zhongshan Hospital of Fudan University between October 2006 and June 2007. MATERIALS Totally 180 female Kunming mice were obtained from the Department of Laboratory Animal, Fudan University. 5-Fu (purity 99%) was purchased from Shanghai Xudong Haipu Pharmaceutical Co, Ltd (Shanghai, China). Two kinds of CS-Pasp-5-Fu particles were offered by Department of Macromolecular Science, Key Laboratory of Molecular Engineering of Polymers of Educational Ministry, Fudan University (Shanghai, China). METHODS: Kunming mice were randomly divided into three groups and each group was administrated with 5-Fu or either type of its CS-Pasp-5-Fu nanoparticlos. The plasma concentrations of 5-Fu were evaluated by high performance liquid chromatography after 15 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours of the administration. The pharmacokinetic parameters were computed utilizing 3P97. MAIN OUTCOME MEASURES: Relative recovery, absolute recovery and the stability of samples. RESULTS: The peak concentration of 5-Fu group occurred within 15 minutes and then decreased rapidly. The No.1 nanoparticles group's peak concentration occurred 6 hours after the administration and the effective concentration time lasted for about 14 hours. No.2 nanoparticles group's concentration curve was double-apex, the apexes occurred around the 2 hours and 16 hours, the concentration decreased at the 24 hours after the administration. Both of the two kinds of the nanoparticles groups' peak concentration of 5-Fu in plasma are lower than the 5-Fu group, The half-life times were prolonged and the areas under curve were higher. CONCLUSION: Compared to 5-Fu, the CS-Pasp-5-Fu nanoparticles are controlled released.