An in vitro model for screening penetration of ocular drug products

筛选眼科药品渗透的体外模型

• 批准号: 10546892
• 负责人: Carrie German
• 金额: $ 30万
• 依托单位: CFD RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546892
• 关键词: Acetates; Anatomy; Animal Model; Anterior; Aqueous Humor; Architecture; Biological Assay; Biological Markers; Cell Culture Techniques; Cell Density; Cell model; Cells; Collagen; Cornea; Data; Development; Devices; Dexamethasone; Dimensions; Drainage procedure; Drug Delivery Systems; Drug Targeting; Endothelial Cells; Endothelium; Epithelial; Epithelial Cells; Evaluation; Exclusion; Exposure to; Extracellular Matrix; Eye; Eyedrops; Fibroblasts; Film; Fluorescein; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Formulation; Goals; Health Sciences; High Pressure Liquid Chromatography; Human; In Vitro; Individual; Injections; Liquid substance; Literature; Medical; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Molecular; Molecular Weight; Morphology; Ocular Physiology; Organ; Penetration; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Physiological; Physiology; Positioning Attribute; Precision therapeutics; Property; Protocols documentation; Rapid screening; Research; Research Personnel; Rhodamine B; Stromal Cells; Testing; Texas; Therapeutic; Thick; Tight Junctions; Time; Tissues; Topical application; Universities; Validation; Visualization; aqueous humor flow; base; clinically relevant; commercialization; conjunctiva; corneal epithelium; density; drug discovery; experience; fluorescein isothiocyanate dextran; hydrophilicity; improved; in vitro Model; in vivo; innovation; lipophilicity; multidisciplinary; multiplex assay; neglect; novel; ophthalmic drug; organ on a chip; phase 1 study; prednisolone; prototype; response; screening; success; targeted treatment

Project Summary/Abstract: The overall objective of this study is to develop a novel, predictive in vitro platform for studying physiological responses of the cellular layers of the anterior eye for therapeutics. Current in vitro models mostly rely on a single cellular architecture of the corneal epithelium and do not mimic the in vivo physiological relevance of cell-cell and cell-ECM interactions. In addition, they lack the capability for real-time visualization and quantitation of cellular interactions. Animal models do not accurately represent the anatomy and physiology of the human eye. We propose to develop and demonstrate a microfluidic-based multicellular architecture of the human cornea based on in vivo morphological and structural parameters. Phase I will culminate with a clear demonstration on the ability of the model to match drug penetration profiles with detailed functional characterization of the cellular interactions and matrix development. During Phase II, we will expand the platform to incorporate additional tissue layers such as the conjunctiva and integration with well plates for a multiplexed assay followed by further validation against in vivo studies. A multi-disciplinary, partnership with expertise in microfluidic cell-based assays, eye physiology and therapeutic screening with clinical relevance has been assembled to successfully meet the research objectives. The end-product will be commercialized to pharmaceutical firms, drug research labs and universities/non-profit centers engaged in precision therapeutics, drug discovery, and drug delivery in the ophthalmic space.

项目摘要/摘要： 本研究的总体目标是开发一种新的、可预测的体外生理学研究平台 眼球前部细胞层对治疗的反应。目前的体外模型大多依赖于单一的 角膜上皮的细胞结构，并不模拟细胞-细胞在体内的生理相关性 以及细胞与细胞外基质的相互作用。此外，它们缺乏实时可视化和量化的能力 细胞间的相互作用。动物模型不能准确地代表人眼的解剖学和生理学。 我们建议开发和展示一种基于微流控技术的人类角膜多细胞结构。 基于体内的形态和结构参数。第一阶段将以明确的演示来结束 该模型将药物渗透曲线与细胞的详细功能特征相匹配的能力 相互作用和矩阵开发。在第二阶段，我们将扩大平台，以纳入更多的组织 层，如结膜，与孔板整合，用于多重分析，随后进一步 对照活体研究进行验证。在微流控电池领域拥有专业知识的多学科合作伙伴关系 与临床相关的化验、眼生理和治疗筛查已成功完成 达到了研究目标。最终产品将商业化给制药公司，药物研究 实验室和大学/非营利性中心从事精确治疗、药物发现和药物输送 眼部的空间。