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A Hybrid Hydrogel Biomaterial by Nanogel Engineering: Bottom-Up Design with Nanogel and Liposome Building Blocks to Develop a Multidrug Delivery System

Authors

  • Yurina Sekine,

    1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
    2. Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan
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  • Yuki Moritani,

    1. Research Laboratories, NTT Docomo Inc., Kanagawa, Japan
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  • Tomoko Ikeda-Fukazawa,

    1. Department of Applied Chemistry, Meiji University, Kanagawa, Japan
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  • Yoshihiro Sasaki,

    1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
    2. PRESTO, Japan Science and Technology Agency, Tokyo, Japan
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  • Kazunari Akiyoshi

    Corresponding author
    1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
    2. Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan
    3. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
    4. ERATO, Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan
    • Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
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Abstract

New hybrid poly(ethylene glycol) (PEG) hydrogels crosslinked with both nanogels and nanogel-coated liposome complexes are obtained by Michael addition of the acryloyl group of a cholesterol-bearing pullulan (CHP) nanogel to the thiol group of pentaerythritol tetra(mercaptoethyl) polyoxyethylene. The nanogel-coated liposome complex is stably retained after gelation and the complexes are well dispersed in the hybrid gel. Microrheological measurements show that the strength and gelation time of the hybrid hydrogel can be controlled by changing the liposome:nanogel ratio. The hydrogel is gradually degraded by hydrolysis under physiological conditions. In this process, the nanogel is released first, followed by the nanogel-coated liposomes. Hybrid hydrogels that can incorporate various molecules into the nanogel and liposomes, and release them in a two-step controllable manner, represent a new functional scaffold capable of delivering multiple drugs, proteins or DNA.

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