A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm<SUP>−2</SUP>) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An <I>in vivo</I> pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics.</P> <P><B>Graphical abstract</B></P> <P>A bio-inspired, self-adherent microneedle (MN) patch is designed for effective transdermal protein drug delivery. The dual-functional MN patch achieved not only a firm adhesion to live animal skin tissue, but also a prolonged insulin drug delivery following a mild loading process into swellable tips with minimal loss of biofunctionality. This transdermal delivery platform using self-adherent MN patches can be applied for a variety of protein drugs requiring sustained release kinetics.</P> <P>[DISPLAY OMISSION]</P>