Closed-Loop Micromotor-Enabled Implantable Drug Delivery System

Implantable drug delivery systems are transforming personalized medicine by enabling localized and controlled therapeutic administration. However, achieving precise, real-time modulation of drug release in response to dynamic physiological conditions remains a significant challenge. Here, we present the development of an implantable nanofluidic micromotor-driven device, capable of modulating in vitro drug release via a temperature-responsive closed-loop system. The device exploits electro-mechanical actuation generated by a micromotor to open and close an integrated channel, enabling controlled drug release. This function is enhanced by a nanofluidic membrane that further regulates molecular transport. The closed-loop system is implemented in a custom-built polystyrene chamber, designed to simulate in vivo thermal conditions. It integrates a heater, fan, temperature sensor, relay module, controller and fluorescence spectrophotometer. A MATLAB algorithm coordinates the entire feedback process, including fluorescence-based drug concentration analysis and temperature regulation via duty cycle control of the heater. In vitro experiments confirmed that drug release takes place exclusively when the micromotor opens the channel, with no detectable release observed when the channel remains closed. This validates the device’s ability to switch drug delivery on and off with high reliability. Additionally, implementation of the closed-loop system enables automated modulation of release in response to thermal input. When the temperature exceeds a set pathological threshold, the system triggers channel opening and drug release. As concentration increases, heater power is reduced, gradually lowering temperature until reaching a physiological threshold, at which point the channel closes and release ceases. In parallel with the in vitro validation, an implantable prototype of the device was also developed, integrating the micromotor valve with an onboard control system composed of a PCB, H-bridge driver, and Bluetooth module. The proposed system offers a novel approach to closed-loop drug delivery, providing robust, adaptive, and precise control over dosing. By mimicking a fever-response model, the device demonstrates strong potential for future in vivo experimentation aimed at validating its therapeutic efficacy and biocompatibility. These findings highlight micromotor-enabled devices as promising tools for next-generation, patient-specific therapeutic strategies.