Depthwise-controlled scleral insertion of microneedles for drug delivery to the back of the eye

Abstract

To treat retinal diseases, intravitreal injection is commonly performed to deliver therapeutic agents to the eye. However, intravitreal injection poses potential risks of ocular complications such as endophthalmitis, retinal detachment, and ocular hemorrhage. Thus, it is desired to develop a minimally invasive and therapeutically effective ocular drug delivery system without full penetration into the sclera. Here, we studied the possibility of precisely-controlled insertion of microneedles (MNs) into the sclera to different levels of depths and how different insertion depths could affect drug delivery into the sclera and to the back of the eye. A microneedle pen (MNP) was developed for depth-controlled scleral delivery by controlling insertion speeds, and it was confirmed that the insertion depths of MNs could be finely controlled by insertion speeds in ex vivo studies. Finite element modeling analyses were also conducted to understand how the depth-controlled insertion of MNs could significantly influence the diffusion distances of drug molecules. Finally, in vivo experiments demonstrated that this MNP system could be applied to the beagle eyes comparable to human ones for the scleral administration of therapeutic agents through the scleral tissues.