Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology
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...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58278-4 |
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| author | Amin GhavamiNejad Jackie Fule Liu Sako Mirzaie Brian Lu Melisa Samarikhalaj Adria Giacca Xiao Yu Wu |
| author_facet | Amin GhavamiNejad Jackie Fule Liu Sako Mirzaie Brian Lu Melisa Samarikhalaj Adria Giacca Xiao Yu Wu |
| author_sort | Amin GhavamiNejad |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f78a494cc0e94e1185aa0ad9de4438a1 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f78a494cc0e94e1185aa0ad9de4438a12025-08-20T03:04:51ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58278-4Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technologyAmin GhavamiNejad0Jackie Fule Liu1Sako Mirzaie2Brian Lu3Melisa Samarikhalaj4Adria Giacca5Xiao Yu Wu6Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of TorontoAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of TorontoAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of TorontoAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of TorontoDepartments of Physiology and Medicine, Institute of Medical Science and Banting and Best Diabetes Centre, Faculty of Medicine, University of TorontoDepartments of Physiology and Medicine, Institute of Medical Science and Banting and Best Diabetes Centre, Faculty of Medicine, University of TorontoAdvanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of TorontoAbstract 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.https://doi.org/10.1038/s41467-025-58278-4 |
| spellingShingle | Amin GhavamiNejad Jackie Fule Liu Sako Mirzaie Brian Lu Melisa Samarikhalaj Adria Giacca Xiao Yu Wu Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology Nature Communications |
| title | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
| title_full | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
| title_fullStr | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
| title_full_unstemmed | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
| title_short | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
| title_sort | catechol based chemistry for hypoglycemia responsive delivery of zinc glucagon via hydrogel based microneedle patch technology |
| url | https://doi.org/10.1038/s41467-025-58278-4 |
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