Assisted 3D printing of microneedle patches for minimally invasive glucose control in diabetes

Recently, microneedle systems have become an attractive solution for drug delivery. Traditionally, microneedle systems were fabricated via template molding methods. In this study, we present a novel method for the fabrication of a microneedle patch system. We used extrusion-based 3D printing and post stretching to fabricate a microneedle patch system for minimally invasive and glucose-responsive insulin delivery for diabetes treatment. First, we investigated the printability of various bioinks composed of alginate with hydroxyapatite as an additive. After printing the substrate and a cylindrical array of the patch, we stretched the top surface of the cylindrical array to form needle-like tips. The prepared microneedle patch contained 6 x 6 microneedles, and only the microneedles performed glucose-responsive release of insulin. Each microneedle was conical in shape, with a base diameter of 601 mu m, a tip diameter of 24 mu m, and a height of 643 mu m. The fabricated microneedles exhibited sufficient mechanical strength to penetrate the skin of mice and responsively released insulin according to the glucose levels both in glucose solution and in type 1 diabetic mice. When transdermal application was performed only once on the skin of mice, the microneedle patches regulated the blood glucose levels of diabetic mice in normoglycemic ranges for up to 40 h and alleviated the diabetic symptoms of the mice. Our study proposed a method for the fabrication of microneedle patch systems, which can be potentially applied for transdermal drug delivery.