Mechanisms of nanostructure-enhanced transepithelial drug delivery

描述(申请人提供)：上皮屏障对大小为20-150 kDa的大分子的输送是一个重大障碍。特别是，连接相邻细胞并封闭细胞旁空间的紧密连接复合体，对大分子的传递构成了显著的障碍。为了改善大分子生物制剂跨上皮细胞的转运，需要开发新的方法，通过特异性和可逆地调节紧密连接来增强细胞旁药物的转运。在这个方案中，我们研究了纳米结构表面在体外对关键治疗分子的紧密连接通透性和运输的调节作用。我们试图确定纳米拓扑术增强上皮通透性的机制，并优化纳米结构材料，以拓宽可以通过细胞外给药的药物类型。预计在这些研究中获得的基础知识将促进新的上皮药物递送系统的开发。

DESCRIPTION (provided by applicant): The epithelial barrier presents a significant obstacle to the delivery of macromolecules in the size range of 20 - 150 kDa. In particular, the tight junctional complex, which links adjacent cells and occludes the paracellular space, presents a significant obstacle to delivery of macromolecules. To improve the transport of macromolecular biologics across epithelia, new approaches need to be developed that enhance paracellular drug transport by specifically and reversibly modulating tight junctions. In this proposal, we investigate the effect of nanostructured surfaces on the modulation of tight junction permeability and transport of key therapeutic molecules in vitro. We seek to determine the mechanisms through which epithelial permeability is enhanced by nanotopography and optimize nanostructured materials to broaden the types of drugs that can be delivered paracellularly. It is expected that the fundamental knowledge gained in these studies will enhance the development of new epithelial drug delivery systems.