Poly(epsilon-caprolactone)-Block-poly(ethyl Ethylene Phosphate) Micelles for Brain-Targeting Drug Delivery: In Vitro and In Vivo Valuation

The purpose of this work was to investigate the potential of poly(epsilon-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 mu g/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 37A degrees 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.