A Wireless Implantable Closed-Loop Electrochemical Drug Delivery System.

Abstract

Wireless implantable drug delivery systems (DDSs) enable targeted, on-demand drug release to maximize therapeutic efficacy. Ultrasound has been proposed to wirelessly power and control millimeter-sized deeply implantable DDSs, but initial demonstrations encountered challenges in power transfer and release control reliability in dynamic in vivo environments. In this work, we present a closed-loop implantable DDS using ultrasound wireless power and communication in conjunction with an electrochemical drug release mechanism. The system consists of piezoelectric transducers for wireless power and data transmission, a drug delivery module containing drug-loaded electroresponsive nanoparticles, and a custom CMOS integrated circuit for closed-loop drug release using a programmable potentiostat capable of providing potentials up to ±1.5 V and sensing current up to ±100 μA. The chip also improves power transfer robustness by enabling ultrasound power combining and rectifier voltage feedback which can be used to adapt the power transmitter and minimize misalignment. Closed-loop release control is tested in vitro using the wirelessly powered DDS at 8 cm depth by adjusting the potentiostat stimulus voltage based on feedback of redox current into fluorescein-loaded nanoparticles, resulting in consistent 2 μg release across different fluorescein loading concentrations and a 39% reduction in release amount variation. These results demonstrate the effectiveness of closed-loop release control in enabling precise and reliable drug delivery.