3D-Printed Microarray Patches for Transdermal Applications

Abstract

The intradermal (ID) space has been actively explored as a means for drug delivery and diagnostics that is minimally invasive. Microneedles or microneedle patches or microarray patches (MAPs) are comprised of a series of micrometer-sized projections that can painlessly puncture the skin and access the epidermal/dermal layer. MAPs have failed to reach their full potential because many of these platforms rely on dated lithographic manufacturing processes or molding processes that are not easily scalable and hinder innovative designs of MAP geometries that can be achieved. The DeSimone Laboratory has recently developed a high-resolution continuous liquid interface production (CLIP) 3D printing technology. This 3D printer uses light and oxygen to enable a continuous, noncontact polymerization dead zone at the build surface, allowing for rapid production of MAPs with precise and tunable geometries. Using this tool, we are now able to produce new classes of lattice MAPs (L-MAPs) and dynamic MAPs (D-MAPs) that can deliver both solid state and liquid cargos and are also capable of sampling interstitial fluid. Herein, we will explore how additive manufacturing can revolutionize MAP development and open new doors for minimally invasive drug delivery and diagnostic platforms.

Figure 1

Routes of delivery. Layers of the skin and drug delivery strategies to access each layer. The epidermal/dermal layers of skin have 1–2 orders of magnitude more immune cells per unit volume of tissue compared to the subcutaneous/muscle layer. IM = intramuscular; SC = subcutaneous; ID = intradermal; MAP = microarray patch. ID access also enables collection of interstitial fluid (ISF). The scale on the right indicates depths of each skin layer. Created using BioRender.

Figure 2

Key MAP design criteria. Created using BioRender.

Figure 3

History of MAP development. A timeline depicting development of MAPs. Generation 1.0 MAPs were made using microfabrication strategies. Generation 2.0 MAPs started to incorporate molding and lithography. Generation 3.0 MAPs are a novel class of MAPs that takes advantage of additive manufacturing strategies to directly fabricate transdermal devices. From left to right, the SEM images are reproduced as follows: Reproduced with permission from ref (47). Copyright 1998 Elsevier. Reproduced with permission from ref (51). Copyright 2006 IOP Science. Reproduced with permission from ref (54). Copyright 2020 Springer Nature. From ref (72). CC BY NC ND. Created using BioRender.

Figure 4

Current landscape of MAPs. MAP technologies that have been employed for transdermal drug delivery and ISF sampling in the past 2 years. (A) Iontophoresis MAPs developed by Yang et al. Adapted with permission from ref (54). Copyright 2020 Springer Nature. (B) Core MAP design by Li et al. Scale bar = 500 μm. Adapted with permission from ref (55). Copyright 2022 Elsevier. (C) Dissolving MAPs by Moon et al. Adapted with permission from ref (56). Copyright 2022 Springer Nature. (D) MAPs for ISF sampling by Samant et al. Scale bar = 200 μm. Adapted with permission from ref (57). Copyright 2020 AAAS. Created using BioRender.

Figure 5

Examples of 3D-printed MAPs. MAPs fabricated using different additive manufacturing strategies for delivery and ISF sampling. (A) MAPs printed using FDM by Wu et al. Adapted with permission from ref (60). Copyright 2020 Elsevier. (B) Hollow MAPs fabricated using mSLA by Xenikakis et al. Adapted with permission from ref (65). Copyright 2022 Elsevier. (C) MAPs made using DLP to sample ISF by Liu et al. Adapted with permission from ref (68). Copyright 2021 Springer Nature. Created using BioRender.

Figure 6

Examples of CLIP 3D-printed MAPs. MAPs fabricated using the CLIP method. (A) Solid MAPs with square pyramidal, conical, arrowhead, and turret geometries by Johnson et al. From from ref (70). CC BY 4.0. (B) Spatial coating of CLIP MAPs using BSA and OVA by Caudill et al. Adapted with permission from ref (71). Copyright 2018 Elsevier. (C) Faceted MAPs with OVA coating made using CLIP by Caudill et al. From ref (72). CC BY NC ND. Scale bars = 500 μm. Created using BioRender.

Figure 7

Lattice MAPs (L-MAPs). (A) L-MAPs are comprised of cells with a cell size and struts with a prescribed strut thickness. (B) L-MAPs can have different projection shapes (square pyramidal or obelisk) as well as different lattice shapes. (C) These parameters can be combined to generate a library of L-MAP designs. Created using BioRender.

Figure 8

SEM images of L-MAPs. SEM images of hi-res CLIP printed L-MAPs with different lattice geometries. L-MAPs were printed using Keysplint Hard resin. Scale bar = 500 μm. CS = cell size; ST = strut thickness. Created using BioRender.

Figure 9

Loading solid and liquid formulations on L-MAPs. (A) Solid state formulations coated and dried on L-MAPs. The SEM images show before and after coating, and a film can be seen after coating. (B) Liquid droplet capture in L-MAPs using red food coloring, shown on an optical microscope. Scale bar = 500 μm. Created using BioRender.

Figure 10

D-MAP designs. (A) Deployment of barbed D-MAP with living hinges. Pushing down deploys the barbs, increasing skin retention. (B) (left) Global stretching of the skin using compliant prongs at the patch level. (right) Local stretching of skin using compliant prongs at the needle level. (C) D-MAP generating pinching/suction to increase ISF sampling from skin. Created using BioRender.