Temperature-Stable Boronate Gel-Based Microneedle Technology for Self-Regulated Insulin Delivery

Insulin delivery in a self-regulated and painless way to tightly control the glycemic level is highly demanded for diabetes treatment. Phenylboronic acid (PBA) has gained great research interests due to its synthetic nature and reversible binding capability with glucose. A totally synthetic smart PBA hydrogel exhibiting efficient glucose sensitivity at physiological pH and temperature has been previously developed. However, its clinical applications may be hampered by the temperature-dependent release profile. Herein, we report a glucose-responsive, temperature-stable, boronate-containing hydrogel with optimized formulation and its fabrication into a microneedle (MN) patch to provide on-demand and convenient insulin delivery. The resulting MN patch displayed temperature-independent and glucose-responsive insulin release in a rapid and sustained manner through the regulation by the "skin layer" formed on the surface. This MNs patch can effectively penetrate the skin and was highly biocompatible. Compared to the majority of the glucose-responsive MN patches capitalizing on glucose oxidase and nanoparticles, this totally synthetic, protein-free, and nanoparticle-free MN patch could eliminate the safety concerns and provide the sustainability and advantage for large-scale production.