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Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology

Author

Listed:
  • Amin GhavamiNejad

    (University of Toronto)

  • Jackie Fule Liu

    (University of Toronto)

  • Sako Mirzaie

    (University of Toronto)

  • Brian Lu

    (University of Toronto)

  • Melisa Samarikhalaj

    (University of Toronto)

  • Adria Giacca

    (University of Toronto)

  • Xiao Yu Wu

    (University of Toronto)

Abstract

Hypoglycemia is a serious and potentially life-threatening condition for people with insulin-dependent diabetes. To provide a safeguard against hypoglycemia, we introduce a “smart” microneedle (MN) patch that senses glucose levels and delivers a blood glucose-raising agent (Zinc-Glucagon (Z-GCN)) in response to hypoglycemia. Herein, we describe the use of catechol and boronic acid chemistry to design a self-crosslinkable hydrogel-based MN that stimulates the release of Z-GCN during hypoglycemia. In this design, the catechol groups bind to Z-GCN through metal-ligand complexation. At hyperglycemia, boronic acids react with glucose to generate cyclic boronate esters. As the glucose concentration decreases, the boronic acid groups dissociate and are favored over Z-GCN in binding with catechol, which promotes the release of Z-GCN. We fully characterize the fabricated MN in vitro. Moreover, we further evaluate the MN and demonstrate the in vivo glucose-responsive delivery of Z-GCN from the patch. We also show its effectiveness in preventing hypoglycemia for up to 6 h in type 1 diabetic male rats against two consecutive insulin overdose challenges. Since many proteins/peptides have a high binding affinity to metal ions, the introduced mechanism driven by the competitive binding of catechol-metal ions has great implications in drug delivery applications of various protein/peptide-based therapeutics.

Suggested Citation

  • Amin GhavamiNejad & Jackie Fule Liu & Sako Mirzaie & Brian Lu & Melisa Samarikhalaj & Adria Giacca & Xiao Yu Wu, 2025. "Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58278-4
    DOI: 10.1038/s41467-025-58278-4
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    References listed on IDEAS

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    1. Sungjin Kim & Abigail U. Regitsky & Jake Song & Jan Ilavsky & Gareth H. McKinley & Niels Holten-Andersen, 2021. "In situ mechanical reinforcement of polymer hydrogels via metal-coordinated crosslink mineralization," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Yuanbo Jia & Jiahui Hu & Keli An & Qiang Zhao & Yang Dang & Hao Liu & Zhao Wei & Songmei Geng & Feng Xu, 2023. "Hydrogel dressing integrating FAK inhibition and ROS scavenging for mechano-chemical treatment of atopic dermatitis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Donglin Gan & Wensi Xing & Lili Jiang & Ju Fang & Cancan Zhao & Fuzeng Ren & Liming Fang & Kefeng Wang & Xiong Lu, 2019. "Plant-inspired adhesive and tough hydrogel based on Ag-Lignin nanoparticles-triggered dynamic redox catechol chemistry," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    4. Shanshan Hu & Xibo Pei & Lunliang Duan & Zhou Zhu & Yanhua Liu & Junyu Chen & Tao Chen & Ping Ji & Qianbing Wan & Jian Wang, 2021. "A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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