Zhang Di, Xu Qian, Liu Ke, Xu Hui
School of Pharmacy, Yantai University, Yantai 264005, China.
Suzhou Nanomedicine R&D Co., Ltd., Suzhou 215123, China.
Zhongguo Zhong Yao Za Zhi. 2016 Oct;41(19):3668-3673. doi: 10.4268/cjcmm20161928.
To investigate the effect of end-capped modification of mPEG-PLA with Boc-phenylalanine(BP) on pharmacokinetic characteristics of curcumin(CUR) loaded micelles, and then provide experimental evidence for prescription optimization. Healthy male SD rats were randomly divided into three groups and they were intravenously administered with a single injection of CUR-mPEG-PLA micelles, CUR-mPEG-PLA-BP micelles and reference formulations DMSO solution(n=6). The doses were 20 mg•kg⁻¹ in term of CUR. Blood samples were collected before and after administration, and the concentration of curcumin in blood plasma was determined by HPLC to draw time-concentration curve. Non-compartmental pharmacokinetic parameters were calculated by using DAS 2.0 software and statistical analysis was conducted between the different groups. The results indicated that the pharmacokinetic characteristics of CUR-mPEG-PLA micelles were similar to those of the free drug of CUR dissolved in DMSO, and the main pharmacokinetic parameters had no significant difference between the two groups. However, as compared with CUR-mPEG-PLA micelles, CUR-mPEG-PLA-BP micelles had a significantly increased area under the time-concentration curve(AUC), significantly prolonged half-life of elimination(tl/2) and mean residence time(MRT), and reduced total body clearance(Cl) (P<0.05). In conclusion, the amphipathic block copolymer of mPEG-PLA-BP could provide curcumin loaded micelles with preferable pharmacokinetic properties in vivo, and CUR-mPEG-PLA-BP micelles were worthy of further research and development.
为研究用Boc-苯丙氨酸（BP）对mPEG-PLA进行封端修饰对载姜黄素（CUR）胶束药代动力学特征的影响，进而为处方优化提供实验依据。将健康雄性SD大鼠随机分为三组，分别单次静脉注射CUR-mPEG-PLA胶束、CUR-mPEG-PLA-BP胶束和参比制剂二甲基亚砜溶液（n = 6）。以CUR计剂量为20 mg•kg⁻¹。给药前后采集血样，采用高效液相色谱法测定血浆中姜黄素浓度，绘制时间-浓度曲线。使用DAS 2.0软件计算非房室药代动力学参数，并对不同组间进行统计分析。结果表明，CUR-mPEG-PLA胶束的药代动力学特征与溶解于二甲基亚砜中的CUR游离药物相似，两组主要药代动力学参数无显著差异。然而，与CUR-mPEG-PLA胶束相比，CUR-mPEG-PLA-BP胶束的时间-浓度曲线下面积（AUC）显著增加，消除半衰期（tl/2）和平均驻留时间（MRT）显著延长，全身清除率（Cl）降低（P<0.05）。综上所述，mPEG-PLA-BP两亲性嵌段共聚物可使载姜黄素胶束在体内具有较好药代动力学性质，CUR-mPEG-PLA-BP胶束值得进一步研发。
