PEDOT-Containing PEG Click-Hydrogel as In Situ Forming Subcutaneous Depot for Electrically-Controlled Insulin Delivery

Managing diabetes is an exhausting and overwhelming task, which has a profound impact in the life of patients. Although insulin (INS) administration has been changing according to the technological developments (infusion sets operated by pumps), patients still have to deal with some inconvenient aspects. Within noninvasive alternatives, injectable in situ forming depots, which are low viscosity injectable polymeric solutions, form a semi-solid polymeric matrix upon injection. If INS is embedded within the matrix, it is feasible to achieve a sustained release, particularly relevant for patients that frequently require INS administration. In this work, we present a click-hydrogel, composed of polyethylene glycol (PEG), as a soft biointerface for INS delivery in which biocompatible poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) have been added to act as the conductive element to facilitate the controlled release of INS over an extended period of time through electrochemical stimulation. The suitable features of these electroactive PEG-based hydrogels have been characterized and include non-swellability, mechanical robustness, stability in an aqueous environment under physiological conditions, excellent cytocompatibility (86% ± 5% viability of L-929 fibroblasts) and straightforward fabrication, which validate their suitability as an injectable in situ forming depot for INS delivery. Moreover, the electrochemical control over INS release and detection has been verified first in cell culture media and, later, with an ex vivo skin mimic. Positive voltage (+0.6 V) increased INS release by ~70% relative to passive conditions, while negative stimulation (−0.6 V) suppressed its release by ~39%. Overall, our biomaterial represents a promising platform for diabetes management, offering precise temporal control via externally applied electrical inputs.