Electroresponsive Thiol-Yne Click-Hydrogels for Insulin Smart Delivery: Tackling Sustained Release and Leakage Control

Andrew Dove, Helena Munoz-Galan, Hamidreza Enshaei, Joao Silva, Teresa Esteves, Frederico Castelo Ferreira, Jordi Casanovas, Josh Worch, Carlos Aleman*, Maria Del Mar Perez Madrigal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

iabetes is a metabolic disorder caused by the body’s inability to produce or use insulin. Considering the figures projected by the World Health Organization, research on insulin therapy is crucial. Hence, we present a soft biointerface based on a thiol–yne poly(ethylene glycol) (PEG) click-hydrogel as an advanced treatment option to administrate insulin. Most importantly, the device is rendered electroactive by incorporating biocompatible poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) as conductive moieties to precisely control the release of insulin over an extended period through electrochemical stimulation (ES). The device has been carefully optimized on account of: (i) the main interactions established between PEDOT- and PEG-based moieties, which have been studied by density functional theory calculations, and reveal the choice of 4-arm PEG precursors as most suitable cross-linkers; and (ii) the concentration of PEDOT NPs in the device, which has been determined considering minimal interference with the gelation process, as well as the resulting morphological, mechanical, electrochemical, and cytocompatible properties of the PEG-based click-hydrogels. Finally, the management over insulin delivery through ES is verified in vitro, with released insulin being detected by high-performance liquid chromatography. Overall, our hydrogel-based device establishes a method for controlled insulin delivery with the potential for translation to other relevant bioelectronic applications.
Original languageEnglish
Pages (from-to)8093–8104
Number of pages12
JournalACS Applied Polymer Materials
Volume6
Issue number14
Early online date11 Jul 2024
DOIs
Publication statusPublished - 26 Jul 2024

Keywords

  • PEDOT nanoparticles
  • insulin delivery
  • click chemistry
  • thiol-yne nucleophilic addition
  • electro-active click hydrogel

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