Improving eye treatment delivery with microneedles

A collaborative team, including scientists from the Terasaki Institute for Biomedical Innovation (TIBI), US, has developed a novel, self-plugging microneedle for injecting therapeutics into the eyes, potentially solving one of the major challenges of treating eye diseases: the accurate delivery of therapeutic drugs to the retina, while guarding against possible complications at the injection site.

Recently published in Advanced Healthcare Materials, the research showed preclinical evidence that this innovative, biodegradable microneedle, dip-coated with a therapeutic drug for release upon insertion into the eyeball, can also be equipped with a special hydrogel that simultaneously seals off the insertion hole. Additionally, this self-plugging microneedle can be fabricated with different needle lengths, so therapeutics can be precisely targeted and dispersed to retinal tissues or other areas within the eyeball.

The team utilised a precision fabrication method to create biodegradable, sharply tipped, ultrathin microneedles of various lengths. This versatility in needle length allowed for a more controllable placement into the eyeball and more accurate drug delivery to the injury site; the fineness of the needles minimise incision size in the eyeball. The sharp end of the needle could be dip-coated with the therapeutic drug, with the needle releasing the drug upon insertion into the eyeball.

As an innovative addition, the blunt end of the microneedle was affixed with an experimentally optimised hydrogel plug, which could swell after needle injection and seal off the insertion hole.

The two microneedle coatings were examined microscopically and tested for strength before subjecting them to validation tests for drug delivery and sealing effectiveness. Initial in vitro tests using the drug-loaded microneedles demonstrated almost complete drug delivery over a 24-hour period; similar experiments using dye-loaded SPNs inserted into vials of pig eyeball fluid demonstrated dye release over a suitable distance for injection into the eyeball.

Ex vivo experiments measuring the internal pressure of cultured pig eyeballs showed that there was almost no change in pressure after applications of SPNs, unlike the pressure drop obtained when non-plugging microneedles were applied. Examination of the tissue at the SPN application site confirmed firm attachment of the SPNs.

Further ex vivo experiments measured dye-tracked release from the SPNs into cultured rabbit and pig eyeballs. Tissue sections from these eyeballs revealed that dye distribution distance from the insertion site was directly proportional to needle length, demonstrating the spatially controllable drug delivery capabilities of the SPNs.

Final tests were conducted in vivo on pig animal models. Seven days after application of dye-loaded SPNs to the pigs’ eyes, observation through the pigs’ corneas revealed that the SPNs were still firmly implanted and there was no needle deformation. Leakage tests using surgical sponges showed no leakage of eyeball fluid.

Tissue section staining of the eyeballs exhibited complete dye dispersal and deep penetration into retinal tissues. Notably, there were no signs of inflammation or tissue disruption at the application site.