Functionalized Polymer Composites for Electrochemical Sensing of Glucose and Smart Insulin Delivery on a Microneedle- Based Platform

Abstract

Advancements in continuous glucose monitoring (CGM) devices combined with readily available insulin pumps have recently enabled development of artificial pancreas device systems that can automatically deliver insulin in response to real-time glucose measurements. Although effective, CGM devices still face challenges in accuracy and stability due to enzymatic detection. In addition, their long solid and metallic needles are not compatible with soft skin and often cause user discomfort. To address these issues, we developed skin-compatible hydrogel microneedle (HMN) electrodes that utilize state-of-the-art conductive and flexible yet mechanically strong polymers to tackle the problems associated with rigid long needles. Via linking dopamine into the backbone of HMN electrodes, we developed an HMN-CGM device based on dopamine's redox properties to generate platinum nanoparticles for non-enzymatic glucose detection. To overcome swelling-related limitations, we developed an enhanced HMN sensor, HMN-P4Au, by incorporating PEDOT:PSS, gold nanoparticles, and polyvinylpyrrolidone. This integration improves sensing capability, mechanical strength, and overall performance reliability. In vivo validation of HMN based CGMs in diabetic rats demonstrated a mean absolute relative difference (MARD) of 12% compared to glucometers, with stable readings maintained over multiple days. Current insulin pumps face challenges due to long needles that cause discomfort and adhesive issues that can lead to detachment, disrupting insulin delivery. To overcome these problems, we developed an HMN embedded with insulin-loaded lipid nanoparticles (LNPs). This design leverages the combined benefits of PEDOT:PSS and dopamine as iontophoresis enhancers. This combination reduces the required iontophoresis voltage to levels compatible with human skin, enabling efficient and safe insulin delivery in form of LNPs. The LNP-insulin formulations, incorporated into microneedle arrays, achieved effective glucose regulation in diabetic rats through a dual-release mechanism. A basal passive release provided sustained insulin delivery, while an active, iontophoresis-triggered release enabled precise glucose control when needed. This combination successfully lowered blood glucose levels to a normoglycemic range without inducing hypoglycemia, demonstrating the potential of this approach for safe and effective diabetes management. Building upon these advancements and via seamless integration of glucose sensing with insulin delivery, this work brings us closer to fully autonomous glucose regulation, offering a promising solution for next-generation diabetes management.