甲氧基聚乙二醇-聚己内酯共聚物载药7-乙基-10-羟基喜树碱纳米粒的制备及药动学参数的测定

Preparation of MePEG-PCL Copolymer Nanoparticles Loaded SN-38 and the Determination of Pharmacokinetics Parameters

目的:制备甲氧基聚乙二醇-聚己内酯(MePEG-PCL)共聚物载药7-乙基-10-羟基喜树碱(SN-38)纳米粒,并测定其在大鼠体内的药动学参数。方法:采用薄膜分散法制备MePEG-PCL共聚物载药SN-38纳米粒。将SD大鼠随机分为两组,分别静脉注射SN-38纳米粒及SN-38溶液制剂(作为对照),采用HPLC法测定两种制剂给药后0.17、0.5、1、2、3、5、7、9、12小时的血药浓度,并用3p97药动学软件处理数据,计算药动学参数。结果:制得的MePEG-PCL共聚物载药SN-38纳米粒粒径为115 nm,包封率大于90%,纳米粒分散液中SN-38质量浓度约为0.2 g.L-1。SN-38纳米粒和SN-38溶液制剂的代谢半衰期(t1/2β)分别为(8.8±1.4)和(1.4±0.3)h;AUC分别为(3.1±0.8)和(1.9±0.5)g.h.L-1。结论:MePEG-PCL嵌段共聚物能够有效包载SN-38。与SN-38溶液制剂相比,MePEG-PCL共聚物载药SN-38纳米粒代谢半衰期更长,AUC更大,表明其具有长循环作用。

Objective： To prepare methoxypoly （ethylene glycol）-polycaprolactone （MePEG-PCL） copolymer nanoparticles loaded SN-38, and to obtain pharmacokinetics parameters from concentration-time data of SN-38 in plasma. Methods： The nanoparticles loaded SN-38 were prepared by the modified thinfilm hydration method. SD rats were randomly divided into two groups, and were administrated SN-38 nanoparticles and SN-38 solution, respectively. The blood sampling was used to determine the contents in plasma of two preparations at 0. 17, 0. 5, 1,2, 3, 5, 7, 9, 12 h by HPLC, and the pharmacokinetics parameters of them were consequently computed by software program 3p97. Results： The nanoparticles were achieved with 0. 2 g· L-1 drug concentration, more than 90% encapsulated efficiency and the size of 115 nm with a narrow size distribution. The biological half-life of SN-38 nanoparticles and S-SN-38 was （8.8 ±1.4） and （1.4 ±0.3） h, respectively, andthe AUC ofthemwas （3.1 ±0.8） and （1.9 ±0.5） g·h·L^-1, respectively. Conclusion： MePEG-PCL copolymers can be efffectively used for loading SN-38, and MePEG-PCL amphiphilic copolymer nanoparticles formulation can be successfully used as a longcirculated intravenous delivery of SN-38, owing to its longer half-life and the bigger AUC than those of SN-38 solution.