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Linear-dendritic polymeric amphiphiles as carriers of doxorubicin—In vitro evaluation of biocompatibility and drug delivery

Authors

  • Zhihua Wu,

    1. State Key Lab on Food Sci&Tech, Jiangxi-OAI Joint Research Institute, Nanchang University, No. 235 Nanjing Rd East, Nanchang 330047, China
    2. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden
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  • Xianghui Zeng,

    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden
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  • Yuning Zhang,

    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden
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  • Neus Feliu,

    1. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Stockholm SE-171 77, Sweden
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  • Pontus Lundberg,

    1. Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, School of Chemical Science and Engineering, Teknikringen 56-58, Stockholm SE-100 44, Sweden
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  • Bengt Fadeel,

    1. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Stockholm SE-171 77, Sweden
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  • Michael Malkoch,

    1. Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, School of Chemical Science and Engineering, Teknikringen 56-58, Stockholm SE-100 44, Sweden
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  • Andreas M. Nyström

    Corresponding author
    1. Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden
    • Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Retzius väg 8, Stockholm SE-171 77, Sweden
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Abstract

In our recent work, we have explored the formation of chemotherapeutic delivery vehicles constructed from four different amphiphilic linear-dendritic hybrid block copolymers. These micelles were found to form about 100-nm-sized structures that were capable of sequestering doxorubicin at loading efficiencies up to 22%. Here, the cellular toxicity of these biocompatible and biodegradable linear-dendritic hybrid materials was evaluated on two breast cancer cell lines and primary human macrophages. The micelles were found not to affect the cellular viability at concentrations below 35 μg mL−1. After drug loading, these constructs could deliver an efficient dose of drugs, resulting in significant decreases in cell viability. Kinetic studies indicated that the drug formulation in the polymer micelles slowed down the cell uptake compared with the nonformulated drug, but similar efficacy in viability reduction and cell apoptosis were found. Taken together, these linear-dendritic hybrid materials represent an interesting novel architecture for the construction of drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

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