biostudies-literatureDinh CTVietnam Ministry of Science and Technology1578https://www.ebi.ac.uk/biostudies/studies/S-EPMC12737151biostudies-literatureUnknown17(12)<b>Background:</b> Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically crosslinked with borax, and evaluated its performance, biosafety, and in vivo efficacy. <b>Methods:</b> MNs were fabricated from PVA/Dextran via micromolding and crosslinked with borax. The formulation was systematically optimized based on mechanical properties and glucose-responsive release kinetics. Physicochemical properties, biosafety (cytotoxicity, skin barrier recovery, boron leaching), and in vivo efficacy in aPharmaceuticsSystematic Development and Characterization of Enzyme-Free, Borax-Crosslinked Microneedles for Glucose-Responsive Insulin Delivery and In Vivo Glycemic Mitigation.PMC12737151ĐTĐLCN.68/22Dinh CTNguyen DTDoan TDNguyen LPPham UTDo HTMNguyen AMLuu PDBui MTHTran TQfalseSystematic Development and Characterization of Enzyme-Free, Borax-Crosslinked Microneedles for Glucose-Responsive Insulin Delivery and In Vivo Glycemic Mitigation.<b>Background:</b> Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically crosslinked with borax, and evaluated its performance, biosafety, and in vivo efficacy. <b>Methods:</b> MNs were fabricated from PVA/Dextran via micromolding and crosslinked with borax. The formulation was systematically optimized based on mechanical properties and glucose-responsive release kinetics. Physicochemical properties, biosafety (cytotoxicity, skin barrier recovery, boron leaching), and in vivo efficacy in a2025-01-01T00:00:00Z2025 Dec2026-05-28T03:14:21.093Z2026-05-28T03:07:05.235ZS-EPMC127371514147109310.3390/pharmaceutics17121578