Microneedles for controlled and sustained intraocular drug delivery

Abstract

Microneedles (MNs) have emerged as a promising technology for minimally invasive drug delivery, offering significant advantages in the treatment of ocular diseases. These miniaturized needles enable precise, localized drug delivery directly into specific tissues of the eye, such as the cornea, sclera, vitreous, or retina, while minimizing pain and discomfort. MNs can be fabricated from various biocompatible materials, including metals, silicon, and biodegradable polymers, making them highly adaptable to various clinical applications. Recent advancements in MN design include the integration of 3D printing technologies to create highly customized geometries for improved drug delivery precision, the use of smart materials that enable stimuli-responsive and sustained drug release, and the development of hybrid microneedles combining different polymers to enhance both mechanical strength and controlled drug release. These innovations have established MNs as a superior alternative to traditional methods like eye drops or intravitreal injections, which often face issues of limited bioavailability and patient compliance. This review summarizes the current state of research on MN-based ocular drug delivery, focusing on material developments, fabrication methods, drug release mechanisms, and implantation techniques. Future directions for MN technology in ophthalmology are also discussed, highlighting its potential to improve treatment outcomes for complex ocular diseases.

Keywords: Biomaterials; Biomedical engineering.

Fig. 1

Schematic overview of MNs for ocular drug delivery.

Fig. 2. Metals and silicon-based MNs.

a Optical microscope (OM) images of a single stainless-steel MN for intrascleral and intracorneal drug delivery. Reproduced with permission from ref. . b OM of stainless-steel MN coated with bevacizumab. Reproduced with permission from ref. . c Scanning electron microscope (SEM) image of fenestrated titanium MN. Reproduced with permission from ref. ^,. d OM of the porous Si needles on a PVA film. Magnified image highlighting the sharpened angular tip of Si needles. Reproduced with permission from ref. . e SEM image of the porous Si needle surface with nanopores. Reproduced with permission from ref. .

Fig. 3. PLA and PLGA-Based MNs.

a Schematic of detachable MN. Reproduced with permission from ref. . b Microscope images of cornea after insertion of detachable MN. Reproduced with permission from ref. . c Schematic structure and concept of MN with sacrificial layer. Reproduced with permission from ref. . d Cryo-sectioned images of MN penetrated the scleral tissue. Reproduced with permission from ref. . e OM of bare, Methacrylated hyaluronic acid and PLGA with Rhodamine coated MN. Reproduced with permission from ref. . f OM of drug distribution depending on the MNs length of 5 mm (left) 15 mm (right). Reproduced with permission from ref. .

Fig. 4. HA-Based MNs.

a Schematic of DL-MNs using MeHA and HA (left) Confocal image DL-MNs loading immunoglobulin G colored with Alexa Fluor 680 (red) and 488 (green) Scale bar: 100 μm (right). Reproduced with permission from ref. . b Drug release distribution images of DL-MNs in agarose hydrogel. Reproduced with permission from ref. . c Time-dependent dissolution of MNs with different PLA contents (Scale bar: 200 μm). Reproduced with permission from ref. . d H&E images of the cornea before and after insertion of 30% PLA MNs (Scale bar: 200 μm). Reproduced with permission from ref. .

Fig. 5. Fabrication methods of MNs for ocular drug deliver.

a Micromolding. Reproduced with permission from ref. . b Electrospinning. Reproduced with permission from ref. . c Drop-born air blowing. Reproduced with permission from ref. . d Centrifugal lithography. Reproduced with permission from ref. . e Electrolithography. Reproduced with permission from ref. . f magnetorheological lithography. Reproduced with permission from ref. .

Fig. 6

Representative drug release mechanisms for ocular drug delivery MNs; diffusion-controlled release, dissolution-controlled release, degradation-controlled release, swelling-controlled release, stimulus-responsive release.

Fig. 7. Implantation methods of MNs into ocular tissues.

a Biodegradable MN patch for corneal healing. Reproduced with permission from ref. . b MNs for ocular drug delivery. Reproduced with permission from ref. . c Contact lens shaped system with silicon nanoneedles for ocular drug delivery. Reproduced with permission from ref. . d Detachable MN pen. Reproduced with permission from ref. .