An in vitro model for screening penetration of ocular drug products

项目概要/摘要： 本研究的总体目标是开发一种新型的预测性体外平台，用于研究生理学 用于治疗的前眼细胞层的反应。目前的体外模型大多依赖于单一的 角膜上皮的细胞结构，并且不模拟细胞-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。第一阶段的高潮将是一个明确的示范， 模型将药物渗透曲线与细胞的详细功能表征相匹配的能力 互动和矩阵发展。在第二阶段，我们将扩大平台，纳入更多的组织 层，如结膜，并与孔板整合，用于多重测定，然后进一步 体内研究验证。一个多学科的合作伙伴关系，具有基于微流体细胞的专业知识， 已经组装了具有临床相关性的检测、眼生理学和治疗筛选， 达到研究目标。最终产品将被商业化的制药公司，药物研究 从事精确治疗、药物发现和药物输送的实验室和大学/非营利中心， 眼空间。

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.