Biodegradable silicon nanoneedles for ocular drug delivery

Abstract

Ocular drug delivery remains a grand challenge due to the complex structure of the eye. Here, we introduce a unique platform of ocular drug delivery through the integration of silicon nanoneedles with a tear-soluble contact lens. The silicon nanoneedles can penetrate into the cornea in a minimally invasive manner and then undergo gradual degradation over the course of months, enabling painless and long-term sustained delivery of ocular drugs. The tear-soluble contact lens can fit a variety of corneal sizes and then quickly dissolve in tear fluid within a minute, enabling an initial burst release of anti-inflammatory drugs. We demonstrated the utility of this platform in effectively treating a chronic ocular disease, such as corneal neovascularization, in a rabbit model without showing a notable side effect over current standard therapies. This platform could also be useful in treating other chronic ocular diseases.

Nanoneedles for targeted siRNA silencing of p16 in the Human Corneal Endothelium

“…Nanoinjection provides efficient, non-immunogenic transfection for different tissues 23 , which was confirmed herein for the non-mitogenic corneal endothelium. Future integration of a flexible nanoneedle substrate to conform to the target tissue alongside optimization of nanoneedle topography and surface chemistry to match cell requirements 21,23 should provide desirable enhancements of transfection efficiency. These optimization steps would also improve the interfacing with the inner surface of the intact cornea, enabling integration of this approach within current corneal endothelium surgery techniques with minor adaptations for in vivo corneal endothelial gene therapy.…”

“…Nanoneedles are a promising approach for corneal delivery, where conventional topical routes are hampered by a drug bioavailability of around 5% that requires large dosing and frequent administration, with risks of severe side effects 21,22 . Silicon nanoneedles integrated in tear-soluble contact lenses are an efficient and painless solution for long-term delivery of ocular drugs 21 . In particular, the corneal endothelium is an appealing target for nucleic acid nanoinjection 4 .…”

Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium

“…Nanoneedles [24] are a promising approach for corneal delivery, where conventional topical routes are hampered by a drug bioavailability of around 5% that requires large dosing and frequent administration, with risks of severe side effects. [25,26] Silicon nanoneedles integrated in tear-soluble contact lenses are an efficient and painless solution for long-term delivery of ocular drugs. [25] The corneal endothelium is an appealing target for nucleic acid nanoinjection [4] and nanoneedles can efficiently transfect siRNA.…”

“…[25,26] Silicon nanoneedles integrated in tear-soluble contact lenses are an efficient and painless solution for long-term delivery of ocular drugs. [25] The corneal endothelium is an appealing target for nucleic acid nanoinjection [4] and nanoneedles can efficiently transfect siRNA. [27][28][29][30] The relative immune privilege of the cornea would reduce the risk of inflammatory response and, since nanoneedles are designed for delivery limited to the superficial layers of a tissue, nanoinjection would selectively reach cells within the corneal endothelial monolayer.…”

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery

“…Electrostimulation, a safe and convenient nonpharmacological therapy/intervention, has been widely exploited to facilitate proliferation and functional development of cells and tissues in tissue engineering and regenerative medicine. − To maximize the therapeutic outcome, electrostimulation treatment is often combined with medications such as tablet, pills, drops, or ointments. − For example, treatment with drugs and electrostimulation has provided augmented analgesia in rat models in comparison to electrostimulation or drugs alone. , A combined treatment using transcutaneous posterior tibial nerve stimulation and trospium chloride provides a better outcome in the treatment of females with overactive bladder in comparison to electrostimulation alone . However, the organic integration of two strategies in one miniaturized system for practical use has seldom been reported.…”