Abstract
Cancer chemotherapy is believed to be impeded by multidrug resistance (MDR) and nonspecific accumulation. This study used methoxy poly-(ethylene glycol) (mPEG, A block) and poly-(ε-caprolactone) (PCL, B block) to synthesize an AB2 type amphiphilic block copolymer to encapsulate the anticancer drug, Doxorubicin (DOX). The molecular weight of copolymer was measured as 19 kDa by a gel permeation chromatography and 15 kDa by proton nuclear magnetic resonance. The amphiphilic block copolymer self-assembled into micelles and critical micelle concentration was 43.7×10− 3 mg/mL. The particle size of empty micelle was 95.1 nm, while it decreased to 21.4 nm after loading with DOX, corresponding to a drug loading efficiency of 22.29%. In the in vitro release experiment, 50% DOX released from the micelles at pH 5 and 40 % at pH 7.4 in 48 hours. The nitric oxide assay indicated that the micelles could avoid recognition by macrophage. Rhodamine 123 assay using flow cytometer showed that the fluorescence of intracellular DOX was stronger in MCF-7/WT than that of MCF-7/ADR. The half lethal dose (IC50) of DOX-loaded micelles for MCF-7/WT and MCF-7/ADR were 0.285 μg/mL and 7.476 μg/mL, respectively. These values are about 7.9-fold higher than the IC50 of free DOX for MCF-7/WT and MCF-7/ADR at 0.036 μg/mL and 0.937 μg/mL, respectively. This can be due to a slow release rate of DOX from micelles. Confocal images showed that DOX-loaded micelles accumulated mostly in the cytoplasm instead of nuclei. On the contrary, free DOX diffused throughout the cells. Flow cytometry histograms indicated that the number of MCF-7/ADR cells under the same fluorescence intensity was about 83.16% and 50.91% for DOX- loaded micelles and free DOX, respectively. In conclusion, the DOX-loaded micelles formed by AB2 copolymer was able to overcome multidrug resistance of breast cancer cells as it can accumulate more in MCF-7/ADR cells compare to free DOX.
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© 2010 International Federation for Medical and Biological Engineering
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Li, Y.L., Chen, Y.T., Cuong, N.V., Hsieh, M.F. (2010). Preparation of Nanoparticles of AB2 Triblock Copolymers for Doxorubicin Delivery. In: Lim, C.T., Goh, J.C.H. (eds) 6th World Congress of Biomechanics (WCB 2010). August 1-6, 2010 Singapore. IFMBE Proceedings, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14515-5_315
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DOI: https://doi.org/10.1007/978-3-642-14515-5_315
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-14514-8
Online ISBN: 978-3-642-14515-5
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