Polyelectrolyte Design Principles for Electrophoretic Drug Delivery

ABSTRACT Soft and tunable materials that facilitate electroactive control over molecular mass transport are key to advancing bioelectronic and therapeutic technologies. Iontronic drug delivery devices rely on polyelectrolytes that act as solid‐state ionic conductors, where drug transport and on‐demand release are controlled by applied electric potentials. Achieving precise dosing requires polyelectrolytes that selectively transport drug‐scale molecules with high conductivity. For drug‐sized molecules > 200 g mol ^{− 1} , achieving these traits simultaneously remains a central challenge that calls for targeted material optimization. Here, we report the design space of polyelectrolytes to improve performance. We systematically varied the composition of AMPS:PEGDA polyelectrolytes and mapped the structure–property–function relationships using a drug‐sized model molecule (cytidine, 243 g mol ⁻¹ ) in relevant device architecture for implantable drug delivery systems. A multiparameter design map identifies quantitative design rules: pair high hydration to sustain transport with balanced fixed charge density to keep loading dynamics manageable, without sacrificing selectivity. Small‐angle X‐ray scattering reveals that nanoscale domain spacing and short‐range order correlate directly with conductivity and efficiency. Optimized formulations outperform previous generations by achieving near‐theoretical delivery efficiencies with minimal sacrifice of ionic conductivity.