Pharmaceutical Research

, Volume 27, Issue 12, pp 2657–2669 | Cite as

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

Research Paper



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 Cmax 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.


biodistribution blood-brain barrier (BBB) micelle polyphosphoester 



The National Basic Research Program of China (2007CB935804 and 2009CB930304), National Natural Science Foundation of China (90713035), and National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”(No 2009ZX09501-024 and 2009ZX09103-066), and Major project of Shanghai Science and Technology Committee (08DZ1980200) are gratefully acknowledged for financial support.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Center of Pharmaceutics, Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
  2. 2.State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
  3. 3.University of Sciences and Technology of ChinaHefeiChina

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