Iron-Responsive Deferasirox Release from Covalently Grafted Hydrogels on Microwires Extends Iron Chelation Time Scales

Implantation of intracortical microelectrodes generates free iron species that exacerbate pro-inflammatory responses by producing reactive oxygen species through the Fenton reaction. This work reports a covalently grafted, two-layer poly(ethylene glycol)dimethacrylate (PEGDMA) hydrogel on polyimide-insulated Pt/Ir microwires for local delivery of the iron chelator deferasirox (DFO). The polyimide insulating layer was methacrylated to enable covalent anchoring of a PEGDMA550 interlayer, followed by a DFO-loaded PEGDMA3400 outer layer. Scanning electron microscopy and optical microscopy of the hydrogel-coated microwires revealed a uniform coating morphology with dispersed DFO aggregates embedded within the matrix. In buffer at 37 °C, DFO release followed diffusion-controlled kinetics and fell below the limit of detection by ultraperformance liquid chromatography by day 9. The iron-chelation properties of the DFO-loaded microwires were investigated using Fe(EDTA) as a free-iron mimic. When a high concentration of Fe(EDTA) was used (10 mM), the Fe(DFO)₂ complex remained detectable for up to 19 days, which expands well beyond the detection limit of DFO under iron-free conditions (9 days). Energy-dispersive X-ray spectroscopy showed time-dependent iron accumulation within the hydrogel, consistent with in-matrix complexation that perturbs local transport and prolongs chelation efficacy. Collectively, the coating functions as a mechanically integrated, responsive reservoir whose pharmacokinetics are governed by the iron concentration rather than initial drug loading. By coupling chelation capacity to local iron availability, the presented hydrogel coating establishes a generalizable route to extend therapeutic lifetimes of functionalized chronic neural electrodes.