Iontophoresis-Integrated Smart Microneedle Delivery Platform for Efficient Transdermal Delivery and On-Demand Insulin Release

Transdermal insulin delivery in a painless, convenient, and on-demand way remains a long-standing challenge. A variety of smart microneedles (MNs) fabricated by glucose-responsive phenylboronic acid hydrogels have been previously developed to provide painless and autonomous insulin release in response to a glucose level change. However, like the majority of MNs, their transdermal delivery efficiency was still relatively low compared to that with subcutaneous injection. Herein, we report an iontophoresis (ITP)-integrated smart MNs delivery platform with enhanced transdermal delivery efficiency and delivery depth. Carbon nanotubes (CNTs) were induced in the boronate-containing hydrogel to develop a semi-interpenetrating network hydrogel with enhanced stiffness and conductivity. Remarkably, ITP not only facilitated efficient and deeper transdermal delivery of insulin via electroosmosis and electrophoresis but also well-maintained glucose responsiveness. This ITP-combined smart MNs delivery platform, which could provide on-demand insulin delivery in a painless, convenient, and safe way, is promising to achieve persistent glycemic control. Furthermore, transdermal delivery of payloads with a wide size range was achieved by this delivery platform and thus shed light on the development of an efficient transdermal delivery platform with deep skin penetration in a minimally invasive way.