A synthetic polymer gel–based insulin delivery device provides an artificial pancreas–like function in healthy and diabetic mice.

Achieving persistent glycemic control in a painless and convenient way is the ultimate goal of diabetes management. Herein, an "enzyme-free" polymeric microneedle (MN)-array patch composed of a boronate-containing hydrogel semi-interpenetrated by biocompatible silk fibroin is developed. Consistent with the previous reports, the presence of the boronate-hydrogel allows for glucose-responsive diffusion-control of insulin, while the crystalline fibroin component serves as a matrix-stiffener to validate skin penetration. Remarkably, this "enzyme-free" smart artificial on-skin pancreas prototype remains stable for at least 2 months in an aqueous environment. Furthermore, it establishes sustained as well as acute glucose-responsive insulin delivery, and is to the authors' knowledge, the first successful material design addressing such two technical challenges at once on an MN format. This long-acting, on-demand insulin delivery technology may offer a candidate for a next-generation diabetes therapy that is remarkably stable, safe, economically efficient, and capable of providing both acute-and continuous glycemic control in a manner minimally dependent on patient compliance.

Microneedle (MN) technology, which can transdermally deliver insulin in a noninvasive manner, offers a promising way to replace subcutaneous self-injection for diabetes management. Hydrogel is an attractive candidate for MN fabrication because of its biocompatibility, controllable degradability, and possibility to achieve sustained as well as stimuli-responsive drug delivery. Herein, we report a smart MN composed of a semi-interpenetrating network (semi-IPN) hydrogel prepared by biocompatible silk fibroin (SF) and phenylboronic acid/acrylamide for glucose-responsive insulin delivery. Six fabrication methods were investigated to maintain the glucose sensitivity of the hydrogel while avoiding deformation during fabrication. The optimized method was to fabricate smart MNs using a two-layer strategy, with a needle region formed by the SF combined semi-IPN hydrogel and the base layer fabricated by SF. The hybrid MN autonomously released insulin well-correspondent to the glucose change pattern via the regulation of the skin layer formed on the surface. Furthermore, this hybrid MN retained its original needle shape after 1 week in aqueous system, thus eliminating the safety concerns associated with dissolving MNs and suggesting the possibility for sustained delivery. This nondegradable smart MN is promising to provide on-demand insulin in a long-acting, painless, and convenient way.

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 temperatureindependent 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.

Recently, phenylboronic acid (PBA) gel containing microneedle (MN) technology with acute and sustained glucose-sensitive functionality has attracted significant research attention. Herein, we report a polyvinyl alcohol(PVA)-coated MNs patch with an interconnected porous gel drug reservoir for enhanced skin penetration efficiency and mechanical strength. The hybrid MNs patch fabricated with a novel, efficient method displayed a “cake-like” two-layer structure, with the tip part being composed of boronate-containing smart gel attached to a porous gel layer as a drug reservoir. The porous structure provides the necessary structural support for skin insertion and space for insulin loading. The mechanical strength of the hybrid MNs patch was further enhanced by surface coating with crystallized PVA. Compared with MNs patches attached to hollow drug reservoirs, this hybrid MNs patch with a porous gel reservoir was shown to be able to penetrate the skin more effectively, and is promising for on-demand, long-acting transdermal insulin delivery with increased patient compliance.