Abstract
PurposeTo apply a simple and flexible manufacturing technique, two-photon polymerisation (2PP), to the fabrication of microneedle (MN) array templates with high precision and low cost in a short time.MethodsSeven different MN array templates were produced by 2PP 3D printing, varying needle height (900–1300 μm), shape (conical, pyramidal, cross-shaped and with pedestal), base width (300–500 μm) and interspacing (100–500 μm). Silicone MN array moulds were fabricated from these templates and used to produce dissolving and hydrogel-forming MN arrays. These polymeric MN arrays were evaluated for their insertion in skin models and their ability to deliver model drugs (cabotegravir sodium and ibuprofen sodium) to viable layers of the skin (ex vivo and in vitro) for subsequent controlled release and/or absorption.ResultsThe various templates obtained with 2PP 3D printing allowed the reproducible fabrication of multiple MN array moulds. The polymeric MN arrays produced were efficiently inserted into two different skin models, with sharp conical and pyramidal needles showing the highest insertion depth values (64–90% of needle height). These results correlated generally with ex vivo and in vitro drug delivery results, where the same designs showed higher drug delivery rates after 24 h of application.ConclusionThis work highlights the benefits of using 2PP 3D printing to prototype variable MN array designs in a simple and reproducible manner, for their application in drug delivery.
Highlights
The use of microneedle (MN) arrays to overcome the limitations of conventional drug delivery has become a growing research field in the past decades
We describe the fabrication of complex and highly detailed MN array master templates using 2PP 3D printing, in a simple and time-effective process which can prove beneficial in comparison with the established template manufacturing techniques previously described
Our results indicated it was important to avoid the use of air pressure or a nitrogen gun to dry the printed structure directly after rinsing with isopropyl alcohol (IPA), as it led to bending of the needle tips
Summary
The use of microneedle (MN) arrays to overcome the limitations of conventional drug delivery has become a growing research field in the past decades These minimally invasive structures, usually comprising multiple micron-sized needles, have shown abilities to deliver a variety of molecules and nanoparticles, for therapeutic and vaccination purposes [1,2]. Throughout the years, MN arrays have been fabricated using a variety of materials, including silicon, metal, ceramics, glass and, more recently, multiple natural and synthetic polymers. For this purpose, researchers have used manufacture techniques mainly emerging from the microelectronics industry, such as reactive ion etching, lithography, electroplating, laser cutting, injection moulding and micromoulding [2]. The majority of polymeric MN arrays are manufactured through mould-based techniques, such as casting, hot embossing, 174 Page 2 of 15
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