壳聚糖-聚天冬氨酸-5氟尿嘧啶纳米的小鼠体内药动学

In vivo research about release of chitosan-polyaspartic acid-5-fluorouracil nanoparticles

目的 5-氟尿嘧啶（5-Fluorouracil，5-FU）原药及其壳聚糖（chitosan，CS）-聚天冬氨酸（polyaspartic acid，Pasp）纳米粒子小鼠灌胃后血药浓度曲线及其药代动力学初步研究。方法同性健康昆明小鼠分为3组，分别予5-FU原药及其2种CS-Pasp纳米粒子灌胃，灌胃后15min，1、2、4、6、8、12、16、24和48h10个时间点颈动脉取血，高效液相色谱法测其血药浓度，代入3P97程序计算各样品的药代动力学参数并作比较。结果 5-FU原药组的药物峰浓度出现在灌胃后15min之内，此后血药浓度迅速降低。CS-Pasp-5FU纳米粒子1组的药物峰浓度出现在灌胃后6h左右，并在较长一段时间内（2～16h）维持较高的浓度。CS-Pasp-5FU纳米粒子2组的血药浓度曲线呈双峰形，药物峰浓度分别出现在灌胃后2h和16h左右，24h后下降。两种CS-Pasp-5FU纳米粒子的血药峰浓度（Cmax）降低，半衰期（f1/2）延长，血药浓度时间曲线下面积（AUC）明显增加。结论 CS-Pasp-5FU纳米粒子有缓释作用。

Purpose To determinate mice plasma concentration curves for 5-fluorouracil （5-FU） and its chitosan （CS）-Polyaspartic acid （Pasp） nanoparticles by high performance liquid chromatography （HPLC） and to investigate their primary pharmacokinetics. Methods Kunming mice were randomly divided into three groups. Each group was administrated with 5-FU or either type of its CS-Pasp nanoparticles. The plasma concentrations of 5-FU were evaluated by HPLC after 15 min,1 h,2 h,4 h,6 h, 8 h,12 h,16 h,24 h and 48 h of the administration to compare their concentration curves and utilize 3P97 to compute their pharmacokinetic parameters. Results The Cmax of 5-FU group occurred within 15 minutes and decreased rapidly. The No. 1 nanoparticles group＇s Cmax occurred 6 h after the administration and the effective concentration time lasted for about 14 h. No. 2 nanoparticles group＇s concentration curve was double-apex, the apexes occurred around the 2^nd hr and the 16^th hr, the concentration decreased at the 24^th hr after the administration. Both of the two kinds of the nanoparticles groups＇ Cmax Of 5-FU in plasma are lower than the 5-FU group, The half-life times（t1/2） were prolonged and the areas under curve（AUC） were higher. Conclusions Compared to 5-FU, its chitosan nanoparticles were controlled released.