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| TITLE | Catechol-based chemistry for hypoglycemia-responsive delivery of zinc-glucagon via hydrogel-based microneedle patch technology |
|---|---|
| AUTHOR | Amin GhavamiNejad, Jackie Fule Liu, Sako Mirzaie, Brian Lu, Melisa Samarikhalaj, Adria Giacca & Xiao Yu Wu |
| YEAR | 2025 |
| JOURNAL | Nature Communications |
| 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. |
| FULL ARTICLE | https://www.nature.com/articles/s41467-025-58278-4 |
| INSTRUMENT | J-810 |
| KEYWORDS | Biomedical materials, Drug delivery, Peptide delivery |
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