An in vitro model for screening penetration of ocular drug products

筛选眼科药品渗透的体外模型

基本信息

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
项目类别：
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

项目摘要

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颖的、预测性的体外平台来研究生理学前眼细胞层对治疗的反应。目前的体外模型大多依赖于单一角膜上皮的细胞结构，不模仿细胞与细胞的体内生理相关性和细胞-ECM 相互作用。此外，他们缺乏实时可视化和定量的能力细胞相互作用。动物模型不能准确代表人眼的解剖结构和生理学。我们建议开发并演示基于微流体的人类角膜多细胞结构基于体内形态和结构参数。第一阶段将以清晰的演示结束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发展。在第二阶段，我们将扩展平台以纳入更多组织结膜等层并与孔板整合以进行多重测定，然后进一步进行针对体内研究的验证。一个多学科的合作伙伴关系，拥有基于微流体细胞的专业知识具有临床相关性的测定、眼生理学和治疗筛选已成功整合达到研究目标。最终产品将商业化给制药公司、药物研究从事精准治疗、药物发现和药物输送的实验室和大学/非营利中心眼科空间。