Poly(ε-caprolactone)-Block-poly(ethyl Ethylene Phosphate) Micelles for Brain-Targeting Drug Delivery: In Vitro and In Vivo Valuation
- 725 Downloads
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.
KEY WORDSbiodistribution 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.
- 9.Ambruosi A, Khalansky AS, Yamamoto H, Gelperina SE, Begley DJ, Kreuter J. Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats. J Drug Target. 2006;14:97–105.CrossRefPubMedGoogle Scholar
- 46.Pardridge WM. Peptide drug delivery to the brain. New York: Raven; 1991. p. 52–3.Google Scholar