Subcutaneous microfuse-activated device for programmed pulsatile drug delivery

Abstract Pulsatile drug delivery, in which rapid drug release is separated by defined lag periods, offers significant therapeutic advantages but is limited by the need for repeated injections and poor patient adherence. Here, we introduce the fused device (FUSED), a subcutaneous system enabling programmed multidose drug delivery through a single implantation. FUSED comprises paired delay and shot units that regulate dosing intervals and trigger pulsatile drug release, respectively. After implantation, body fluids gradually dissolve the microfuse in each delay unit, with the delay duration determined by fuse length. Once fluid reaches a shot unit, an effervescent reaction is initiated, producing rapid drug release. In vitro and in vivo evaluations demonstrated precise pulsatile release of the model antigen ovalbumin, effectively reproducing prime–boost vaccination timing and eliciting the corresponding immune response. These results suggest that FUSED may provide a viable alternative to repeated injections and improve adherence in multidose therapeutic regimens.