双修饰壳聚糖载丝裂霉素C纳米粒在大鼠体内的药动学研究

Pharmacokinetics of Dual Conjugated Chitosan-mitomycin C Nanoparticles in Rats

目的研究双修饰壳聚糖载丝裂霉素C纳米粒在大鼠体内的药动学特征。方法2组大鼠分别静脉注射4mg·kg^-1丝裂霉素C纳米粒和丝裂霉素C注射剂后，采用高效液相色谱-串联质谱法（HPLC-MS）测定给药后不同时间点血浆中丝裂霉素C的浓度，计算主要药动学参数。结果丝裂霉素C的线性范围20-1000μg·L^-1，最低定量限为20μg·L^-1，提取回收率均〉95％，日内、日间精密度RSD均〈15％。双修饰壳聚糖载丝裂霉素C纳米粒和丝裂霉素C注射剂t1／2分别为（2．64±0．11）h、（0．49±0．049）h；AUC0-∞分别为（2．01±0．11）mg·h·L-1、（0．93±0．075）mg·h^-1·L^-1；Vz分别为（1．52±0．18）L、（0．63±0．065）L；CL分别为（6．95±0．70）mL·min^-1、（15．47±1．89）mL·min^-1，2者均有显著性差异。结论该方法灵敏、准确、专一，适用于丝裂霉素C的药动学研究。与丝裂霉素C注射剂相比，双修饰壳聚糖栽丝裂霉素C纳米粒具有缓释和长循环的作用。

OBJECTIVE To study the pharmacokinetics of dual conjugated chitosan-mitomycm C nanopartlcles （CS-MMC-NPs） in rats. METHODS The two groups of rats were injected with CS-MMC-NPs and MMC injection at the dose of 4 mg·kg^-1. The concentrations of MMC in plasma at different time were determined by HPLC-MS and the main pharmacokinetic parameters were calculated. RESULTS The calibration curves were linear over the range of 20-1 000 μg·L^-1. The limit of quantitation was 20 μg·L^-1. The within day and day to day relative standard deviation（RSD） was 〈15%. The main pharmacokinetic parameters of CS-MMC-NPs and MMC injection were as follows： t1/2 were （2.64±0.11）h and （0.49±0.049）h, AUC0-∞ were （2.01±0.11）mg·h^-1·L^-1 and （0.93±0.075）mg·h^-1·L^-1, Vz were （1.52±0.18）L and （0.63±0.065）L, CL were （6.95±0.70）mL.min 1 and （15.47±1.89）mL·min^-1. The differences of parameters were significant between two preparations. CONCLUSION The method is sensitive, accurate, specific for the pharmacokinetic study of CS-MMC-NPs. Compared with MMC injection, CS-MMC-NPs has a controlled releasing rate, a high level of blood concentrations and a long blood circulation time, which benefits the control of acute toxicity of MMC for the rats.