Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)-diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.