Preparation of phenylboronic acid-based hydrogel microneedle patches for glucose-dependent insulin delivery

There is a problem with directly loading insulin into the polymerized glucose-responsive microneedle (MN) patch due to that polymerization conditions and solvents may damage the activity of insulin. In this study, we report a totally polymerized phenylboronic acid-based MN patch, and insulin was directly loaded in MNs by a mild drop/dry procedure. MN patch was prepared by copolymerization of N -isopropyl acrylamide, N -vinyl-2-pyrrolidone, and 3-acrylamidoephenylboronic acid in MN mold. The MN patch showed good glucose-dependent swelling behavior in pH 9.0 at 27°C. After insulin loading procedure, insulin was distributed on and within the MNs. About 43.2% of total insulin was diffused into MNs' interior. As a result, the release of insulin on MNs' surface was uncontrolled by MNs and rapidly finished after ~10 min. However, the release of insulin within MNs was depended on glucose concentration, and insulin was released 1.6 times more at 4 g/L than at 1 g/L glucose concentration after 12 h. Although further improvements are needed to make MN patch responding in physiological environment, this work suggests a solution for directly loading insulin in polymerized glucose-responsive MNs.