A double-layer transdermal insulin delivery platform combining a sodium hyaluronate microneedle patch and a conductive hydrogel for electrically controlled release

Transdermal delivery of macromolecular drugs offers significant potential for continuous and stable administration in chronic disease management. We developed a non-invasive double-layer transdermal insulin delivery platform integrating a sodium hyaluronate (SH) dissolvable microneedle (MN) patch and a conductive hydrogel both loaded with insulin, featuring multiple release kinetics with rapid passive release and electro-driven controlled release. By varying initial concentration and molecular weight (Mw) of the SH, the mechanical properties of the MN patches could become optimized to a Young's modulus of 138.5 ± 3.0 MPa), exceeding 3 times the maximum failure stress of the stratum corneum, thereby ensuring efficient puncture and delivery properties at the same time. A conductive hydrogel was developed as second layer, composed of quaternized chitosan grafted with polyaniline (QCP), polyvinyl alcohol (PVA) and borate (BA), that undergoes dynamic crosslinking via borate ester groups and ionic interactions, which possesses well-controlled electric conductivity and viscoelastic properties. Under the influence of the electric field, the internal reticular structure of the hydrogel accelerates dissociation, thereby increasing the drug release rate. In vitro models demonstrated that the MN patch effectively established transport channels and enabled rapid insulin release, providing the necessary conditions for transdermal delivery of the conductive hydrogel layer and accelerating transport efficiency. Meanwhile, the electro-driven mode could enhance the insulin delivery rate by 225% and maintained continuous, stable and efficient release behavior over the 24-h treatment period.