Abstract
Microneedles, arrays of micron-sized needles that painlessly puncture the skin, enable transdermal delivery of medications that are difficult to deliver using more traditional routes. Many important design parameters, such as microneedle size, shape, spacing, and composition, are known to influence efficacy, but are notoriously difficult to alter due to the complex nature of microfabrication techniques. Herein, we utilize a novel additive manufacturing (“3D printing”) technique called Continuous Liquid Interface Production (CLIP) to rapidly prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio, spacing). This technology allows for mold-independent, one-step manufacturing of microneedle arrays of virtually any design in less than 10 minutes per patch. Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate, polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and polycaprolactone were fabricated to demonstrate the range of materials that can be utilized within this platform for encapsulating and controlling the release of therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine.
Highlights
Microneedle patches are arrays of sharp, sub-millimeter-sized needles that enhance transdermal drug delivery by physically perforating the tough outer layer of the skin to enable a therapeutic of interest to more pass into the body. [1,2] Unlike hypodermic needles, microneedles are small enough that they avoid nerve endings buried deep within the skin; PLOS ONE | DOI:10.1371/journal.pone.0162518 September 8, 2016Additive Manufacturing of Microneedles competing interests: JRT, DS, AE, and JMD all have an equity stake in Carbon, Inc., which is a venturebacked startup company
We report rapid additive manufacturing of microneedle arrays from trimethylolpropane triacrylate and the biocompatible materials polyethylene glycol dimethacrylate, polycaprolactone trimethacrylate, and polyacrylic acid
To assess feasibility of applying Continuous Liquid Interface Production (CLIP) to microneedle production, we investigated the fabrication of microneedles using a model resin composed of trimethylolpropane triacrylate (TMPTA mixed with 2.5wt% diphenyl (2,4,6- trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator
Summary
Microneedle patches are arrays of sharp, sub-millimeter-sized needles that enhance transdermal drug delivery by physically perforating the tough outer layer of the skin to enable a therapeutic of interest to more pass into the body. Additive Manufacturing of Microneedles competing interests: JRT, DS, AE, and JMD all have an equity stake in Carbon, Inc., which is a venturebacked startup company. This does not alter our adherence to PLOS One policies on data sharing and materials. [1,2,3] Microneedles enable transdermal drug delivery of a range of therapeutics that are difficult to deliver orally, such as proteins,[4] nucleic acids, [5] and large, hydrophobic molecules.[6]. Many pharmacokinetic profiles are achievable, providing improved control of therapeutic concentrations to maximize efficacy while minimizing side effects. [11,12,13]
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