Development of Nanoneedle Array for Painless and Long-Term Sustained Intraocular Drug Delivery

开发用于无痛、长期持续眼内药物输送的纳米针阵列

• 批准号: 10280693
• 负责人: Chi Hwan Lee
• 金额: $ 39.63万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10280693
• 关键词: Address; Affinity; Area; Binding; Blindness; Blood Vessels; Blurred vision; Chemistry; Choroidal Neovascularization; Chronic; Clinical; Complex; Contact Lenses; Cornea; Corneal Neovascularization; Custom; Development; Disease; Dose; Drainage procedure; Drops; Drug Compounding; Drug Delivery Systems; Dry Eye Syndromes; Effectiveness; Engineering; Extravasation; Eye; Eyedrops; Fluorescein Angiography; Gold; Histology; Hour; Human; Immunohistochemistry; In Vitro; Infection; Inflammation; Inflammatory; Keratoplasty; Kinetics; Lasers; Liquid substance; Low-Level Laser Therapy; Mechanics; Modeling; Morphology; Nature; Needles; Operative Surgical Procedures; Oryctolagus cuniculus; Pain; Painless; Patients; Performance; Pharmaceutical Preparations; Photography; Polymers; Porosity; Property; Radial; Research; Retinal Neovascularization; Risk; Risk Factors; Shapes; Silicon; Structure; Surface; Surgical sutures; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Translating; Trauma; Treatment Efficacy; Validation; Vascular Endothelial Growth Factors; Water; base; biomaterial compatibility; cell injury; chemical conjugate; clinical implementation; clinical practice; crystallinity; design; drug release profile; improved; in vivo; in vivo Model; in vivo evaluation; innovation; limbal; miniaturize; minimally invasive; nanofabrication; nanomaterials; nanoneedle; nanoscale; programs; prototype; side effect; standard care; stem cells; tool; water solubility

PROJECT SUMMARY/ABSTRACT Corneal neovascularization (CNV), or the invasion of new blood vessels into the avascular cornea, remains one of the major causes of blindness worldwide. Topical eye drop therapy serves as the most easily accessible and noninvasive treatment of CNV, but its therapeutic efficacy is limited due to the corneal barriers and nasolacrimal drainage that quickly eliminates eye drops within a few minutes. Recent advances of biodegradable microneedles have led to the development of many strategies for intraocular drug delivery through the corneal barriers, which increases therapeutic efficacy. However, the clinical implementation of these microneedles in human eyes is often impeded due to their relatively large size for the human cornea and rapidly dissolving nature (typically, within 15 minutes-2 hours), which causes pain and limited therapeutic efficacy, respectively. The research endeavors of this project will focus on the development of a new class of intraocular drug delivery platform made from fully-miniaturized (i.e., at nanoscale) and slowly-biodegradable silicon nanoneedles that are > 30-fold smaller and provide > 10-fold slower degradation rate compared to current biodegradable microneedles. The silicon nanoneedles will be built upon a water-soluble contact lens that offers excellent biocompatibility, softness, rapid degradability in tear fluid (within no more than 30 seconds), and optimal curvature to fit a variety of corneal shapes (8.3-9.0 mm base curve radii). These aspects are essential to allow for the minimally-invasive, painless, and long-term (over days) sustained delivery of ocular drugs through the corneal barriers. In this project, we will reveal the structure-property-performance relationship of the silicon nanoneedles with various size, shape, aspect ratio, and surface porosity in vitro and ex vivo. We will also evaluate the biosafety, therapeutic efficacy, and side-effects of the silicon nanoneedles in a well-established rabbit CNV model in vivo, as compared to conventional anti-vascular endothelial growth factor therapy (anti- VEGF) and laser therapy. Because the materials used for both the nanoneedles and water-soluble contact lens are already in clinical use, this intraocular drug delivery platform can be rapidly translated into clinical practice for the treatment of CNV in human eyes. Furthermore, the established intraocular drug delivery platform will be also useful for the treatment of other chronic ocular diseases, including corneal, retinal, and choroidal neovascularization.

项目概要/摘要 角膜新生血管（CNV），或新血管侵入无血管的角膜，仍然存在 全世界失明的主要原因之一。局部滴眼液疗法是最容易获得的 以及CNV的无创治疗，但由于角膜屏障和角膜屏障等原因，其治疗效果有限。 鼻泪管引流可在几分钟内快速消除眼药水。可生物降解材料的最新进展 微针导致了许多通过角膜进行眼内药物输送的策略的发展 屏障，从而提高治疗效果。然而，这些微针的临床应用 由于人类角膜的尺寸相对较大以及快速溶解的性质，人眼经常会受到阻碍 （通常在 15 分钟至 2 小时内），这分别会导致疼痛和有限的治疗效果。这 该项目的研究工作将集中于开发新型眼内药物输送 由完全小型化（即纳米级）且可缓慢生物降解的硅纳米针制成的平台 与目前的可生物降解材料相比，尺寸小 30 倍，降解速度慢 10 倍 微针。硅纳米针将建立在水溶性隐形眼镜的基础上，提供优异的 生物相容性、柔软性、在泪液中快速降解（不超过30秒）、最佳 曲率适合各种角膜形状（基弧半径 8.3-9.0 毫米）。这些方面对于允许 通过微创、无痛、长期（数天）持续输送眼部药物 角膜屏障。在这个项目中，我们将揭示硅的结构-性能-性能关系 体外和离体具有各种尺寸、形状、纵横比和表面孔隙率的纳米针。我们还将 以成熟的方法评估硅纳米针的生物安全性、治疗功效和副作用 兔体内 CNV 模型，与传统的抗血管内皮生长因子治疗（抗血管内皮生长因子治疗）相比 VEGF）和激光治疗。因为纳米针和水溶性隐形眼镜所用的材料 已投入临床使用，该眼内给药平台可快速转化为临床实践 用于治疗人眼 CNV。此外，已建立的眼内药物递送平台将 也可用于治疗其他慢性眼部疾病，包括角膜、视网膜和脉络膜 新血管形成。