ABSTRACT
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.