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Abstract Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid–liquid phase separation that protects unstable proteins. A three‐layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three‐phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi‐drug therapies through a single treatment.
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Cleanroom‐Free Fabrication of Microneedles for Multimodal Drug Delivery
Abstract Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high‐resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low‐cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink‐molding of hydrogels to form high‐resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.
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- PAR ID:
- 10405820
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Small
- Volume:
- 19
- Issue:
- 29
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Hollow microneedles are extremely attractive to drug delivery domains with high demands from clinics and industry. However, its complicated fabrication processes have impeded its wide adoption. This paper presents a simple one-step fabrication method for hollow microneedles based on diffraction UV lithography and solid-liquid light propagation. The fabrication process utilizes bottom-up exposure of a liquid photosensitive resin through photomask patterns comprising a plurality of apertures. Hollow microneedles with various heights were fabricated in a range of 400 µm to 600 µm from a few minutes of UV exposure. The fabricated hollow microneedles were characterized with force-displacement tests showing a good tip strength of 0.35 N per single unit. A hollow fluidic test on a pig cadaver skin showed great potential for drug delivery. Also, batch fabrication with multiple height microneedles on a single substrate has demonstrated compatibility with the manufacturing process.more » « less
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