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

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ABSTRACT

Purpose

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.

Method

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.

Results

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.

Conclusion

These results suggest that PCL-PEEP micelles could be a promising brain-targeting drug delivery system with low toxicity.

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ACKNOWLEDGEMENTS

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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Authors and Affiliations

  1. Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China

    Pengcheng Zhang & Yaping Li

  2. State Key Laboratory of Drug Research Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China

    Luojuan Hu & Linyin Feng

  3. University of Sciences and Technology of China, Hefei, 230026, China

    Yucai Wang & Jun Wang

Authors
  1. Pengcheng Zhang
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  2. Luojuan Hu
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  3. Yucai Wang
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  4. Jun Wang
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  5. Linyin Feng
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  6. Yaping Li
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Corresponding authors

Correspondence to Linyin Feng or Yaping Li.

Additional information

Pengcheng Zhang and Luojuan Hu contributed equally to this work.

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Zhang, P., Hu, L., Wang, Y. et al. Poly(ε-caprolactone)-Block-poly(ethyl Ethylene Phosphate) Micelles for Brain-Targeting Drug Delivery: In Vitro and In Vivo Valuation. Pharm Res 27, 2657–2669 (2010). https://doi.org/10.1007/s11095-010-0265-9

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  • DOI: https://doi.org/10.1007/s11095-010-0265-9

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