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      An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

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          Abstract

          Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy.

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          Author and article information

          Journal
          Acta Biomater
          Acta biomaterialia
          Elsevier BV
          1878-7568
          1742-7061
          Dec 2017
          : 64
          Affiliations
          [1 ] Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072, China.
          [2 ] Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
          [3 ] Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China. Electronic address: wwwangtj@163.com.
          [4 ] Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
          [5 ] Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072, China. Electronic address: jhuazhang@tju.edu.cn.
          Article
          S1742-7061(17)30616-5
          10.1016/j.actbio.2017.09.044
          28974477
          0b6af050-8295-4352-93a9-b709c59e92f8
          History

          Glucose-responsive,Injectable hydrogel,Insulin delivery,Microsphere,Tissue-adhesive

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