Continuous Liquid Interface Production of Microneedles for Transdermal Drug Delivery Public Deposited

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Last Modified
  • March 20, 2019
Creator
  • Johnson, Ashley
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
Abstract
  • The past two decades of microneedle research has demonstrated the benefits of microneedle technology in transdermal drug delivery. Microneedles are arrays of sub-millimeter sized projections that physically pierce the outer layer of the skin to allow a therapeutic to pass into the body. Using microneedles to create physical channels within the skin has enabled transdermal delivery of many medications that would otherwise need be delivered by hypodermic injection. Because microneedles are so small that they evade nerve endings buried deep within the skin, they have enabled pain free delivery of medications, providing an opportunity for improved patient compliance. Biocompatible microneedles are of particular interest because they are thermodynamically stable at room temperature, safe for patients and enable controlled release of medication out of the patch. The micro-manufacturing processes used to manufacture such biocompatible microneedles, however, do not allow for control over critical microneedle design parameters, such as size, shape, aspect ratio and spacing. Herein, we utilize a novel additive manufacturing technique called Continuous Liquid Interface Production (CLIP) to manufacture microneedles for transdermal drug delivery. This technique is that fastest microneedle fabrication technique in the world, to date, and enables unprecedented control over patch design parameters. We show that CLIP microneedles can be produced in under 2 minutes per patch and demonstrate capability to produce microneedle designs that cannot be fabricated using other mold-based techniques, such as arrowhead microneedles. CLIP microneedles were produced from more than four different compositions, including photopolymerizable derivatives of biocompatible materials designed to dissolve, degrade, or swell within the skin to release a cargo. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine. Further, the mechanical properties of these microneedle devices are investigated using polyethylene glycol (PEG) with varying crosslink densities. We demonstrate that the elastic modulus of these hydrogels is a critical design parameter that influences microneedle insertion into the skin. Stiff microneedles are shown to effectively penetrate porcine skin ex vivo with lower application forces, whereas more rubbery microneedles require a greater force to effectively insert into the skin.
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Rights statement
  • In Copyright
Advisor
  • DeSimone, Joseph M.
  • Lai, Samuel
  • Jay, Michael
  • Oldenburg, Amy
  • Huang, Leaf
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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