Microneedles (MN) have emerged as an innovative technology for drug delivery, offering a minimally invasive approach to administer therapeutic agents. Recent applications have included ocular drug delivery, requiring the manufacture of sub-millimeter needle arrays in a reproducible and reliable manner. The development of 3D printing technologies has facilitated the fabrication of MN via mold production, although there is a paucity of information available regarding how the printing parameters may influence crucial issues such as sharpness and penetration efficacy. In this study, we have developed and optimized a 3D-printed MN micro-mold using stereolithography (SLA) 3D printing to prepare a dissolving ocular MN system. The effects of a range of parameters including aspect ratio, layer thickness, length, mold shape and printing orientation have been examined with regard to both architecture and printing accuracy of the MN micro-mold, while the effects of printing angle on needle fidelity was also examined for a range of basic shapes (conical, pyramidal and triangular pyramidal). Mechanical strength and in vitro penetration of the polymeric (PVP/PVA) microneedles produced from reverse molds fabricated using MN with a range of shapes and height, and aspect ratios was assessed, followed by ex vivo studies of penetration into excised scleral and corneal tissue. The optimization process identified the parameters required to produce MN with the sharpest tips and highest dimensional fidelity, while the ex vivo studies indicated that these optimized systems would penetrate the ocular tissue with minimal applied pressure, thereby allowing ease of patient self-administration.

Microneedles (MNs) have attracted considerable interest as a means of ocular drug delivery, a challenging delivery route due to the limitations imposed by the various biological barriers associated with this organ. In this study, a novel ocular drug delivery system was developed by formulating a dissolvable MN array containing dexamethasone-loaded PLGA microparticles for scleral drug deposition. The microparticles serve as a drug reservoir for controlled transscleral delivery. The MNs displayed sufficient mechanical strength to penetrate the porcine sclera. Dexamethasone (Dex) scleral permeation was significantly higher than in topically instilled dosage forms. The MN system was able to distribute the drug through the ocular globe, with 19.2% of the administered Dex detected in the vitreous humour. Additionally, images of the sectioned sclera confirmed the diffusion of fluorescent-labelled microparticles within the scleral matrix. The system therefore represents a potential approach for minimally invasive Dex delivery to the posterior of the eye, which lends itself to self-administration and hence high patient convenience.

This study evaluates the ocular toxicity and therapeutic efficacy of a dissolvable microneedle (MN) system containing PLGA nanoparticles loaded with dexamethasone (Dex) using a rabbit model of endotoxin-induced uveitis. Previous research by our group demonstrated the potential of MN systems in delivering PLGA microparticles to scleral tissue. Building on this, we conducted an in-vivo study to assess the irritancy and therapeutic activity of Dex-loaded nanoparticles in MN patches. Results showed that both Blank-MN and Dex-MN patches caused minimal irritation, with no mechanical injury upon insertion. Dex-MN patches had a lower irritation score, and faster recovery compared to Blank-MN patches. In the uveitis model, Dex-MN patches significantly reduced clinical scores of uveitis and levels of pro-inflammatory markers (TNF-α, IL-6, MPO), and normalized apoptosis mediators (Bax, BCL2, NF-κB, Caspase3). Histopathological assessments confirmed reduced inflammatory reactions and cellular in-filtrate in Dex-MN treated eyes. These findings indicate that the Dex-loaded dissolvable MN system is a safe and effective platform for ocular drug delivery, offering significant therapeutic benefits in treating ocular inflammation.