Smart ultra-long-lasting sequentially triggerable and artfully implantable nozzle system for on-demand drug delivery for chronotherapy.

Conventional drug delivery methods for chronic disease often suffer from low potency and poor patient compliance, while current advanced devices face limitations because of bulkiness, frequent implantation needs, inflammation risk, and lack of precise control. To overcome these challenges, we developed the SUSTAIN-a smart, ultra-long-lasting, sequentially triggerable, and artfully implantable nozzle system. The SUSTAIN integrates an osmotic pressure-triggered module, an airflow-generated T-pipe (AGT), and a drug infusion pump (DIP) for controlled subcutaneous drug release. The AGT enables tunable dosing by varying NaHCO(3)/KH(2)PO(4) powder amounts, while shear thinning of the β-cyclodextrin/Pluronic F-127 hydrogel in the DIP ensures sustained drug infusion. In vivo studies show that the SUSTAIN delivers at least four doses of levothyroxine sodium over 10 days and three doses of semaglutide over 42 days, maintaining effective blood drug levels with minimal invasiveness. This system presents a highly promising solution for improving therapeutic outcomes and convenience in chronic disease management.