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<p>The nuclear envelope serves as a highly regulated gateway for macromolecule exchange between the nucleus and cytoplasm in eukaryotes. Here we have developed a cell nucleus-mimicking polymeric membrane-enclosed system for long and self-regulated therapy. A polymeric nano-membrane with nanopores is conformally synthesized in situ on the surface of each insulin crystal, ensuring sustained, adjustable and zero-order drug release kinetics. Glucose- and β-hydroxybutyrate-dually sensitive microdomains are integrated into the nano-membranes. Under a normal state, the microdomains are uncharged and the channel is narrow enough to block insulin outflow. Under hyperglycaemia and ketonaemia, microdomains convert the high glucose and β-hydroxybutyrate concentration signals to the negative electric potential of membranes, widening the nanopores with rapid insulin outflow. In type 1 diabetic mice and minipigs, this system can maintain normoglycaemia for longer than 1 month and 3 weeks, respectively, with validated glucose- and β-hydroxybutyrate-triggered insulin release. Such membrane-enclosed drug crystal/powder formulation provides a broad platform for long-acting controlled release.</p>

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A bioinspired polymeric membrane-enclosed insulin crystal achieves long-term, self-regulated drug release for type 1 diabetes therapy

  • 期刊论文

  • 发表日期：

    2025年2月26日

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  • Jianchang Xu,
  • Yang Zhang,
  • Sheng Zhao,
  • Juan Zhang,
  • Yanfang Wang,
  • Wei Liu,
  • Kangfan Ji,
  • Guangzheng Xu,
  • Ping Wen,
  • Xinwei Wei,
  • Shaoqian Mei,
  • Leihao Lu,
  • Yuejun Yao,
  • Feng Liu,
  • Yufei Ma,
  • Jiahuan You,
  • Jianqing Gao,
  • John B. Buse,
  • Jinqiang Wang,
  • Zhen Gu

摘要

The nuclear envelope serves as a highly regulated gateway for macromolecule exchange between the nucleus and cytoplasm in eukaryotes. Here we have developed a cell nucleus-mimicking polymeric membrane-enclosed system for long and self-regulated therapy. A polymeric nano-membrane with nanopores is conformally synthesized in situ on the surface of each insulin crystal, ensuring sustained, adjustable and zero-order drug release kinetics. Glucose- and β-hydroxybutyrate-dually sensitive microdomains are integrated into the nano-membranes. Under a normal state, the microdomains are uncharged and the channel is narrow enough to block insulin outflow. Under hyperglycaemia and ketonaemia, microdomains convert the high glucose and β-hydroxybutyrate concentration signals to the negative electric potential of membranes, widening the nanopores with rapid insulin outflow. In type 1 diabetic mice and minipigs, this system can maintain normoglycaemia for longer than 1 month and 3 weeks, respectively, with validated glucose- and β-hydroxybutyrate-triggered insulin release. Such membrane-enclosed drug crystal/powder formulation provides a broad platform for long-acting controlled release.