槲皮素PLGA嵌段共聚物纳米粒冻干粉针剂在大鼠体内的药动学分析

目的:考察槲皮素聚乳酸-羟基乙酸共聚物(PLGA)嵌段共聚物纳米粒冻干粉针剂在大鼠体内的药动学过程,为槲皮素制剂的开发与利用提供参考。方法:采用HPLC测定槲皮素在大鼠体内的血药浓度,流动相甲醇-4.3%乙酸溶液(75∶25),检测波长254 nm,比较槲皮素PLGA嵌段共聚物纳米粒冻干粉针剂和槲皮素静脉注射乳剂的生物等效性。结果:槲皮素PLGA嵌段共聚物纳米粒针剂在大鼠体内的主要药动学参数为药峰浓度(Cmax)16.129 mg·L-1,消除半衰期(t1/2)7.384h,清除率(clearance,CL)0.362 L·h-1·kg-1,时量曲线下面积(AUC0-t)99.461 mg·L-1·h-1。在相同给药剂量下,乳剂组和纳米粒组的主要药动学参数均存在极显著性差异,槲皮素纳米粒组的消除半衰期为乳剂组的1.52倍,有利于增加药物与肿瘤患处细胞的接触时间,提高药物抗癌的疗效,槲皮素纳米粒较乳剂的相对生物利用度172.92%。结论:槲皮素PLGA嵌段共聚物纳米粒针剂明显改变了槲皮素的药物动力学行为,药物消除减慢,同时提高了药物的生物利用度,在治疗肿瘤切除术后残留癌灶方面具有广阔应用前景。

Pharmacokinetic Analysis of Quercetin-PLGA Block Copolymer Nanoparticles Lyophilized Powder in Rats

Objective: To detect pharmacokinetics process of quercetin-poly(lactic-co-glycolic acid)(PLGA) block copolymer nanoparticles lyophilized powder in rats,then provide a reference for development and utilization of quercetin preparation. Method: HPLC was employed to determine plasma concentration of quercetin in rats with mobile phase of methanol-4.3% acetic acid solution(75: 25) and detection wavelength at 254 nm,bioequivalence of quercetin-PLGA block copolymer nanoparticles lyophilized powder and intravenons emulsion was compared. Result: Main pharmacokinetic parameters of quercetin-PLGA block copolymer nanoparticles in mice displayed that Cmax 16.129 mg · L^-1,t1/2 7.384 h,CL 0.362 L · h^-1 · kg^-1,AUC_0-t 99.461 mg · L^-1 · h^-1.At the same dose,main pharmacokinetic parameters of the quercetin emulsions group and the quercetin nanoparticles group were highly significant differences.Elimination half-life of the quercetin nanoparticles group was 1.52 times of the quercetin emulsions group.Compared with quercetin emulsions,relative bioavailability of quercetin nanoparticles was 172.92%. Conclusion: Quercetin-PLGA block copolymer nanoparticles significantly change pharmacokinetic behavior of quercetin,drug elimination time slows down,while bioavailability increases.It has a broad application prospects in anti-tumor,especially in treatment of tumor resection of residual disease.