Hybrid Microneedle Arrays for Intradermal and Transdermal Delivery

<p dir="ltr">This work investigates the design, production, and assessment of hybrid microneedle arrays (MNAs) for intradermal drug delivery, integrating the advantages of dissolvable and hollow microneedles. Hybrid MNAs consist of a sharp tip made from a dried, biodissolvable polymer gel and a rigid non-dissolvable microcannula stem, from which drug solutions can be infused into the skin after penetration. Hybrid MNAs offer a dynamic platform for minimally invasive, biphasic drug administration by overcoming limitations in existing microneedle technologies, including limited drug delivery capacity of dissolvable MNAs and blockage of holes after insertion of hollow MNAs. The study encompasses an extensive assessment of design factors, material choices, production techniques, and performance evaluations, resulting in the creation of a scalable manufacturing system for future clinical and commercial use.</p><p dir="ltr">The design procedure utilizes finite element analysis to enhance geometric factors to ensure mechanical integrity and efficient skin penetration. The material selection emphasizes biocompatibility, mechanical strength, and manufacturability, employing thermoset epoxy resin for the microneedle shafts and water dissolvable hydrogels formulated from a variety of polymers and sugars for the tips. Comprehensive testing is undertaken to refine hydrogel compositions, achieving a balance between speedy dissolution, adhesion, and mechanical strength.</p><p dir="ltr">Additionally, a novel manufacturing strategy integrating mechanical micromilling and multi-stage micromolding processes to produce highly accurate MNAs is presented. This highly flexible fabrication approach is capable of facilitating rapid prototyping and manufacturing of geometrically intricate and reproducible microneedles from a variety of materials. The fabricated MNAs undergo thorough geometric evaluation, confirming the reproducibility and accuracy of the fabrication technique. Experimental and simulation-based evaluations validate the devices' capacity to endure insertion forces without deformation or failure. Functional assays in agar-based skin phantoms and ex vivo human skin models exhibit efficient tip dissolving and demonstrate drug delivery capability. In vivo applications employing fluorescent markers also verify the biphasic delivery capability of hybrid MNAs, enabling localized and accurate intradermal deposition.</p><p dir="ltr">A robotic-assisted high-throughput manufacturing method enabling the production of thousands of MNAs daily is also presented. The technology incorporates automated dispensing, centrifugation, and optical quality control in a modular assembly line, ensuring high accuracy and reproducibility. This innovation greatly decreases variability and production time, tackling a major obstacle to clinical and commercial adoption.</p><p dir="ltr">The results underscore the capacity of hybrid MNAs to improve cutaneous drug delivery by offering a compelling alternative to traditional intradermal delivery methods like the Mantoux technique, offering simplified administration that requires minimal clinical training. The technology exhibits high mechanical performance, fast disintegration, and reliable drug delivery, establishing it as a critical instrument for many medical applications such as vaccine administration.</p>