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: 10673052
• 负责人: Chi Hwan Lee
• 金额: $ 38.26万
• 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/10673052
• 关键词: Address; Affinity; Anti-Inflammatory Agents; 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; Eye diseases; Eyedrops; Fluorescein Angiography; Growth; Histology; Hour; Human; Immunohistochemistry; In Vitro; Infection; Inflammation; Invaded; 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; Retina; Risk; Risk Factors; Shapes; Silicon; Structure; Surface; Surgical sutures; Techniques; Testing; Therapeutic; Time; Tissues; Translating; Trauma; Treatment Efficacy; Validation; Vascular Endothelial Growth Factors; Visual; 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; prototype; side effect; standard care; stem cells; technology platform; 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.

项目总结/文摘

项目成果

Multimodal In Vivo Imaging of Retinal and Choroidal Vascular Occlusion.

视网膜和脉络膜血管闭塞的多模态体内成像。

• DOI: 10.3390/photonics9030201
• 发表时间: 2022
• 期刊: Photonics
• 影响因子: 2.4
• 作者: Nguyen,VanPhuc;Zhu,Tianye;Henry,Jessica;Zhang,Wei;Wang,Xueding;Paulus,YannisM
• 通讯作者: Paulus,YannisM