Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Pharm Res. 2010 Dec;27(12):2657-69. doi: 10.1007/s11095-010-0265-9. Epub 2010 Sep 18.
The purpose of this work was to investigate the potential of poly(ε-caprolactone)-block-poly(ethyl ethylene phosphate) (PCL-PEEP) micelles for brain-targeting drug delivery.
The coumarin-6-loaded PCL-PEEP micelles (CMs) were prepared and characterized. The cellular uptake of CMs was evaluated on in vitro model of brain-blood barrier (BBB), and the brain biodistribution of CMs in ICR mice was investigated.
PCL-PEEP could self-assemble into 20 nm micelles in water with the critical micelle concentration (CMC) 0.51 μg/ml and high coumarin-6 encapsulation efficiency (92.5 ± 0.7%), and the micelles were stable in 10% FBS with less than 25% leakage of incorporated coumarin-6 during 24 h incubation at 37°C. The cellular uptake of CMs by BBB model was significantly higher and more efficient than coumarin-6 solution (CS) at 50 ng/ml. Compared with CS, 2.6-fold of coumarin-6 was found in the brains of CM-treated mice, and C(max) of CMs was 4.74% of injected dose/g brain. The qualitative investigation on the brain distribution of CMs indicated that CMs were prone to accumulate in hippocampus and striatum.
These results suggest that PCL-PEEP micelles could be a promising brain-targeting drug delivery system with low toxicity.
本研究旨在探讨聚（ε-己内酯）-嵌段-聚（乙基乙烯基磷酸酯）（PCL-PEEP）胶束用于脑部靶向药物传递的潜力。
制备并表征了香豆素-6 负载的 PCL-PEEP 胶束（CMs）。在体外血脑屏障（BBB）模型上评估了 CMs 的细胞摄取，研究了 CMs 在 ICR 小鼠中的脑内分布。
PCL-PEEP 可在水中自组装成 20nm 的胶束，临界胶束浓度（CMC）为 0.51μg/ml，香豆素-6 的包封效率高达 92.5±0.7%，且在 37°C孵育 24 小时内，在含有 10%胎牛血清的条件下，胶束稳定，包载的香豆素-6 泄漏率小于 25%。与 CS 相比，50ng/ml 时 BBB 模型对 CMs 的细胞摄取明显更高、更有效。与 CS 相比，CM 处理组小鼠脑内香豆素-6 的含量增加了 2.6 倍，CM 的 C(max)为注射剂量/g 脑的 4.74%。CMs 在脑内分布的定性研究表明，CMs 易于在海马和纹状体蓄积。
这些结果表明，PCL-PEEP 胶束可能是一种具有低毒性的有前途的脑部靶向药物传递系统。
