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A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin
Seong, Keum-Yong,Seo, Min-Soo,Hwang, Dae Youn,O'Cearbhaill, Eoin D.,Sreenan, Seamus,Karp, Jeffrey M.,Yang, Seung Yun Elsevier 2017 Journal of controlled release Vol.265 No.-
<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>
Touch-actuated transdermal delivery patch for quantitative skin permeation control
Kim, Bongsoo,Seong, Keum-Yong,You, Insang,Selvaraj, Veerapandian,Yim, Sang-Gu,O’Cearbhaill, Eoin D.,Jeong, Unyong,Yang, Seung Yun Elsevier 2018 Sensors and actuators. B Chemical Vol.256 No.-
<P><B>Abstract</B></P> <P>With increasing demands on drug delivery <I>via</I> a transdermal route, there is a therapeutic and regulatory need for on-demand dosage control. Ideally, on-demand dose control would be based on a low-cost, scalable mechanical mechanism without the requirement for ancillary equipment. In this study, we report a touch-actuated transdermal delivery (TATD) patch which provides quantitative permeation control by the degree of mechanical pressing. The patch contains a refillable drug solution reservoir, strain sensor, and drug chamber with an array of microneedles. Mathematical functions are used to predict the normal force applied to the drug reservoir, drug solution released into the drug chamber, and amount of the permeated drug. The final relationship between permeation level and normal force is expressed as a simple equation, which allows for the precise control of drug permeation <I>via</I> external mechanical stimulation. This relationship is demonstrated by image analysis of the permeated drug through animal skin tissue. The TATD patch offers a suitable platform for on-demand control of therapeutic delivery in wearable healthcare systems.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A touch-actuated transdermal delivery (TATD) patch providing quantitative permeation control by mechanical pressing has been developed. </LI> <LI> Mathematical functions are used to predict the normal force applied to the drug reservoir, drug solution released into the drug chamber, and amount of the permeated drug. </LI> <LI> The relationships are clarified by release tests and <I>ex vivo</I> skin penetration tests <I>via</I> the permeated drug through animal skin tissue. </LI> </UL> </P>