Two-Photon Polymerisation 3D Printing of Microneedle Array Templates with Versatile Designs: Application in the Development of Polymeric Drug Delivery Systems

Abstract

Purpose To 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. Methods Seven 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. Results The 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. Conclusion This 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.

Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion

“…For example, OCT was recently used to image the insertion of MN arrays manufactured using a two-photon polymerization technique [ 127 ]. In this study, OCT was used to measure the percentage of needles inserted into PF, an established model membrane used for MN insertion studies as discussed previously [ 127 ]. Furthermore, successful MN insertion into full-thickness neonatal porcine skin was also illustrated using OCT.…”

“…This rapid prototyping technology can be useful for optimization studies which require testing of different designs and/or materials in a short amount of time [ 212 ]. Recently, such an approach was used in a comparative study [ 127 ]. The performances of various MNs heights, shapes, and separation on the penetration and drug-releasing characteristics of different biodegradable polymer blends were examined.…”

3D-printed microneedles in biomedical applications

“…Longer MNs possess a more efficient drug deposition rate, due to the deeper penetration into skin, with lower mechanical strength. In addition, by increasing the interspacing of MNs, although, because of the reduced number of MNs per array, the overall amount of delivered drug decreases, the drug delivery efficiency improves ( Cordeiro et al., 2020 ). Besides the delivery of the substances to the treatment area, it is important to penetrate MN without damaging the surroundings in the sensitive organs.…”

Microarray patches enable the development of skin-targeted vaccines against COVID-19

“…Solid microarrays are also utilized as master molds to fabricate inverse or negative molds (also known as production molds) for the manufacturing of other MAP types, such as dissolvable, porous, and hybrid MAPs [ 216 , 226 , 245 , 256 ]. Traditional microfabrication techniques (e.g., etching and photolithography) have been broadly used to create solid MAPs; however, new approaches, such as micromachining, diamond micromilling, and most recently 3D printing, have emerged to address the material, geometry, ramp-up time, and cost limitations of cleanroom-based microfabrication strategies [ 216 , 228 , 229 , 257 ]. Notably, 3D printing, or additive manufacturing, approaches have drawn considerable recent attention due to their unprecedented design flexibility, which enables fabrication of more innovative microarray geometries [ 230 , 231 , 258 , 259 ].…”