Combining rapid and sustained insulin release from conducting hydrogels for glycemic control

• Published in: European polymer journal Vol. 181; p. 111670
• Main Authors: Muñoz-Galán, Helena, Molina, Brenda G., Bertran, Oscar, Pérez-Madrigal, Maria M., Alemán, Carlos
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.12.2022; Elsevier BV
• Subjects: Chemical compounds; Conducting polymer; Control systems; Controlled release; Diabetes; Drug delivery systems; Electrostimulation; Glutamic acid; Hydrogel; Hydrogels; Insulin; Molecular dynamics; Nanoparticles; Time; Molecular dynamics; Diabetes; Hydrogel; Conducting polymer; Electrostimulation
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2022.111670

[Display omitted] •Two systems with identical components have been prepared for insulin release.•Despite their chemical resemblance, they exhibit very different release profiles.•In one, the release is rapid by diffusion and the rest by external stimulation.•In the other, the release is slow by degradation of the carrier.•The combination of the two system might allow a complete glycemic control. Innovative insulin delivery systems contemplate combining multi-pharmacokinetic profiles for glycemic control. Two device configurations have been designed for the controlled release of insulin using the same chemical compounds. The first insulin delivery system, which displays a rapid release response that, in addition, is enhanced on a short time scale by electrical stimulation, consists on an insulin layer sandwiched between a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) film and a poly-γ-glutamic acid (γ-PGA) hydrogel. The second system is constituted by γ-PGA hydrogel loaded with insulin and PEDOT nanoparticles by in situ gelation. In this case, the insulin release, which only starts after the degradation of the hydrogel over time (i.e. on a long time scale), is slow and sustained. The combination of an on-demand and fast release profile with a sustained and slow profile, which act on different time scales, would result in a very efficient regulation of diabetes therapy in comparison to current systems, allowing to control both fast and sustained glycemic events. Considering that the two systems developed in this work are based on the same chemical components, future work will be focused on the combination of the two kinetic profiles by re-engineering a unique insulin release device using γ-PGA, PEDOT and insulin.