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: 10480936
• 负责人: Chi Hwan Lee
• 金额: $ 37.11万
• 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/10480936
• 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; Persons; 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.

项目摘要/摘要 角膜新血管形成（CNV）或新血管入侵血管角膜，仍然存在 全球失明的主要原因之一。局部眼药疗法是最容易获得的 和CNV的无创治疗，但由于角膜屏障和 鼻腔表引流，可以在几分钟内迅速消除眼部滴。可生物降解的最新进展 微针已导致开发了许多通过角膜的眼内药物递送的策略 障碍，增加了治疗功效。但是，这些微针的临床实施 由于人的角膜相对较大和迅速溶解性质，人们的眼睛通常受到阻碍 （通常在15分钟至2小时内），这会导致疼痛和有限的治疗功效。这 该项目的研究努力将集中于开发新的眼内药物输送 由全次分配的平台（即在纳米级）和缓慢降解的硅纳米制成的平台 与当前的可生物降解相比 微针。硅纳米德犬将建立在水溶性的隐形眼镜上，该隐形眼镜提供出色 生物相容性，柔软度，泪液中的快速降解性（不超过30秒）和最佳 曲率适合各种角膜形状（8.3-9.0毫米基曲线半径）。这些方面对于允许 对于微不足道的，无痛和长期（几天）的持续递送眼药的侵入性 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 纳米果具有各种大小，形状，纵横比和表面孔隙率的体外和外体。我们也会 评估硅纳米元素的生物安全，治疗功效和副作用 与常规的抗血管内皮生长因子治疗相比，体内兔CNV模型（抗 VEGF）和激光疗法。因为用于纳米果和水溶性隐形眼镜的材料 这项眼内药物输送平台已可以迅速转化为临床实践 用于治疗人眼中的CNV。此外，已建立的眼内药物输送平台将是 也可用于治疗其他慢性眼疾病，包括角膜，视网膜和脉络膜 新血管形成。