Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery

Abstract

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.

Glucose‐Responsive Insulin and Delivery Systems: Innovation and Translation

“…In addition, a glucose-responsive transdermal patch for insulin delivery was also demonstrated. [51] Another approach to improve the glucose-responsive performance in the physiological environment is to introduce new components into polymer structures. For example, a hydrogel composed of both crosslinked and grafted poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) [poly(NIPAMco-AAPBA)] exhibited glucose-triggered volume expansion at 37 °C and pH 8.8.…”

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…MN patches fabricated using a hydrogen peroxide-labile copolymer encapsulating insulin and glucose oxidase, were able to release insulin under hyperglycemic conditions (Zhang et al, 2018b). In contrast, enzyme-free glucose-responsive MN array for insulin delivery was achieved by a using boronate hydrogel and biocompatible silk fibroin for fabrication (Chen et al, 2019). Another example of targeted delivery was the delivery of STAT3 siRNA for the treatment of melanoma by dissolving polyethylenimine MNs (Pan et al, 2018).…”

Polymeric Microneedle Arrays: Versatile Tools for an Innovative Approach to Drug Administration

“…[28] The MN format made this on-demand insulin delivery long-acting, stable, safe, economically efficient, and capable of providing both acute and continuous glycemic control without depending on patient compliance. [28] The MN format made this on-demand insulin delivery long-acting, stable, safe, economically efficient, and capable of providing both acute and continuous glycemic control without depending on patient compliance.…”

“…In vivo (human) [24] Melasma Dissolving In vivo (mouse) [25] Acne vulgaris Swelling In vivo (mouse) [26] Ocular infection Dissolving Ex vivo (cornea) [27] Diabetes Swelling In vitro In vivo (mouse) [28] [ 29] Cancer Dissolving In vitro In vivo (mouse) [30] [ 31,43] Immunity (vaccines)…”