Fenestrated microneedles for ocular drug delivery

The development of a safe, simple, and efficacious means for ocular drug delivery remains a critical unmet need. Solid microneedles (MNs) show significant promise in this regard. However, the limited drug carrying capacity of devices demonstrated to date may limit potential for clinical translation, due to the prohibitively large array sizes that may be required for delivery of therapeutically relevant dosages. In this study, titanium deep reactive ion etching (Ti DRIE) is used to address this limitation via fabrication of MNs with complex through-thickness fenestrations (i.e., windows), which serve as reservoirs for passive delivery. Using finite element analyses, mechanical testing, and ex vivo rabbit cornea preparations, we show that these devices possess sufficient stiffness for reliable insertion. Furthermore, using spectrophotometry and fluorescence microscopy, we show that these devices can increase carrying capacity up to five-fold relative to solid MNs of comparable size, as well as enhance sub-surface deposition in ex vivo rabbit cornea. Collectively, these results begin to demonstrate the potential embodied in fenestrated Ti MNs for eventual realization of ocular drug delivery devices with more clinically relevant form factors. (C) 2015 Elsevier B.V. All rights reserved.