Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Department of Rheumatology and Immunology, State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Nanjing Drum Tower Hospital, Southeast University, Nanjing, 210096, China.
J Nanobiotechnology. 2024 Sep 28;22(1):588. doi: 10.1186/s12951-024-02851-4.
Riboflavin-5-phosphate (riboflavin) is the most commonly used photosensitizer in corneal crosslinking (CXL); while its efficient delivery into the stroma through the corneal epithelial barrier is challenging. In this paper, we presented novel responsive porous microneedles with ocular microinjection capability to deliver riboflavin controllably inside the cornea to facilitate CXL. The microneedle patch was composed of Poly (N-isopropyl acrylamide) (PNIPAM), graphene oxide (GO), and riboflavin-loaded gelatin. After penetrating the cornea by the stiff and porous gelatin needle tip, the photothermal-responsive characteristic of the PNIPAM/GO hydrogel middle layer could realize the contraction of the gel under the stimulation of near-infrared light, which subsequently could control the release of riboflavin from the backing layer into the cornea stromal site both in vitro and in vivo. Based on the microneedles system, we have demonstrated that this microinjection technique exhibited superior riboflavin delivery capacity and treatment efficacy to the conventional epithelial-on protocol in a rabbit keratoconus model, with benefits including minimal invasiveness and precise administering. Thus, we believe the responsive porous microneedles with riboflavin ocular microinjection capability are promising for clinical corneal crosslinking without epithelial debridement.
核黄素 5-磷酸（核黄素）是角膜交联术（CXL）中最常用的光敏剂；然而，将其有效地递送至基质层穿过角膜上皮屏障是具有挑战性的。在本文中，我们提出了一种具有眼部微注射能力的新型响应性多孔微针，以将核黄素可控地递送至角膜内部，从而促进 CXL。微针贴片由聚（N-异丙基丙烯酰胺）（PNIPAM）、氧化石墨烯（GO）和负载核黄素的明胶组成。在坚硬且多孔的明胶针尖穿透角膜后，PNIPAM/GO 水凝胶中间层的光热响应特性可以在近红外光的刺激下实现凝胶的收缩，随后可以控制从背衬层将核黄素递送至角膜基质部位的释放，无论是在体外还是体内。基于微针系统，我们已经证明，与传统的上皮保留方案相比，这种微注射技术在兔角膜圆锥模型中表现出了优异的核黄素递送能力和治疗效果，具有微创和精确给药的优点。因此，我们相信具有核黄素眼部微注射能力的响应性多孔微针有望用于临床角膜交联术，而无需进行上皮清创。
