Mechanisms of nanostructure-enhanced transepithelial drug delivery

摘要 上皮屏障是大分子转运的重要障碍。 大小范围为20-150 kDa。尤其是连接相邻细胞的紧密连接复合体 并堵塞细胞旁间隙，对输送 大分子。为了改善大分子生物制品在上皮细胞中的运输，新的 需要开发方法，通过具体和有效的方法来加强细胞旁药物的转运 可逆地调节紧密连接。在这项建议中，我们调查了 纳米结构表面对密结渗透性和传输键的调制作用 治疗分子在体外。我们试图确定上皮细胞 通过纳米拓扑术增强渗透性，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。预计基本面 在这些研究中获得的知识将促进新的上皮药物输送的开发 系统。

ABSTRACT 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.