Polymeric 3D-Printed Microneedle Arrays for Non-Transdermal Drug Delivery and Diagnostics

Abstract

Microneedle arrays (MNAs) are becoming increasingly popular due to their ease of use and effectiveness in drug delivery and diagnostic applications. Improvements in three-dimensional (3D) printing techniques have made it possible to fabricate MNAs with high precision, intricate designs, and customizable properties, expanding their potential in medical applications. While most studies have focused on transdermal applications, non-transdermal uses remain relatively underexplored. This review summarizes recent developments in 3D-printed MNAs intended for non-transdermal drug delivery and diagnostic purposes. It includes a literature review of studies published in the past ten years, organized by the target delivery site-such as the brain and central nervous system (CNS), oral cavity, eyes, gastrointestinal (GI) tract, and cardiovascular and reproductive systems, among other emerging areas. The findings show that 3D-printed MNAs are more adaptable than skin-based delivery, opening up exciting new possibilities for use in a variety of organs and systems. To guarantee the effective incorporation of polymeric non-transdermal MNAs into clinical practice, additional research is necessary to address current issues with materials, manufacturing processes, and regulatory approval.

Keywords: 3D printing; diagnostics; drug delivery; microneedle arrays; non-transdermal applications.

Figure 1

Fabrication and morphological characterization of PmSL SLA 3D-printed MNA. (A) As-printed MNA structure, (B) fully assembled device with inkjet-printed conductive paths for three-electrode electrochemical sensing, (C) scanning electron microscopy (SEM) image showing the details of the MNA, (D) high-magnification SEM image of a single MN illustrating its fine tip resolution, essential for effective tissue penetration. Reprinted under a Creative Commons Attribution 3.0 Unported license [43].

Figure 2

Schematic illustration of the working principles of key 3D printing techniques used for polymeric MNA fabrication: (A) SLA, (B) DLP, (C) LCD, (D) SOPL, (E) 2PP, (F) FDM.

Figure 3

Schematic illustration of the 4D printing and post-processing workflow for barbed MNAs. (i) A pristine resin is selectively photopolymerized to form a crosslinked network, while uncured monomers remain in the structure. (ii) Rinsing removes the uncured monomers, leading to (iii) desolvation-driven shrinkage. (iv) Drying induces stress gradients across the cured regions, causing programmed bending deformation. (v) A final UV post-curing step fixes the structure into its backward-facing, curved barb configuration. Reproduced with permission from Wiley [95].

Figure 4

A developed MNA system for drug delivery to the brain. (A) Schematic illustration of the application of integrating MNA–capillary assemblies with nanoinjector systems to facilitate MNA-mediated simultaneous, distributed microinjections of target fluidic substances/suspensions into brain tissue. (B–D) SEM images of the fabricated MNA with different magnifications. (E) Experimental setup for the evaluation of the drug delivery capability of the developed MNAs, including the MNA–capillary assembly interfaced with a custom-built nanoinjector and an excised mouse brain on ice. (F) Sequential images of a representative MNA penetration, microinjection, and retraction process for a surrogate fluid (blue-dyed deionized water) injected into brain tissue. (G) Magnified view of the postinjection site. Adopted with permission from Wiley [17].

Figure 5

A developed MNA for drug delivery to the oral cavity. (A) Morphology of hydrogel MNA. (B,C) SEM images of the needle of the fabricated MNA with different magnifications. (D) Drug release profile showing that approximately 3.2% of madecassoside was released within 6 h, totaling 7.73 mg. (E) Effect of hydrogel MNA extracts on cell viability, showing a decrease of about 15% at day 3, which represented the lowest observed viability. Adopted under a CC-BY license [75].

Figure 6

(A) Stages of capsule function, from ingestion to deployment and eventual excretion. (B) Schematic of the magnetic actuation mechanism, illustrating how the cantilever deploys in response to an external magnetic field. (C) Detailed view of cantilever (i) before deployment, (ii) during the deployment of drug-loaded MNAs into the tissue, and (iii) during the subsequent release of the drug. (D) Photograph of the fully assembled capsule. (E) Close-up of the dissolvable microneedle array designed to release the drug into GI tissue upon deployment. Reprinted with permission from Cell Press [119].

Figure 7

Schematic and experimental validation of the DOAMS MNA tablet system for gastric drug delivery. (A) Diagram showing pH-triggered deployment and anchoring of the tablet in the stomach. (B) SEM image of MNA. (C) Illustration of tablet delivery in pigs. (D,E) Plasma semaglutide profiles showing enhanced absorption with DOAMS compared to control tablets. Reprinted under a CC BY license [123].