Mechanisms of nanostructure-enhanced transepithelial drug delivery

描述（由申请人提供）：上皮屏障对20 - 150kda大小的大分子的递送存在重大障碍。特别是紧密的连接复合物，它连接相邻的细胞并阻塞细胞旁空间，对大分子的递送构成重大障碍。为了改善大分子生物制剂在上皮间的运输，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运输。在本研究中，我们在体外研究了纳米结构表面对紧密连接通透性和关键治疗分子转运的调节作用。我们试图确定通过纳米形貌增强上皮通透性的机制，并优化纳米结构材料，以扩大可以通过细胞旁递送的药物类型。预计在这些研究中获得的基础知识将促进新的上皮给药系统的发展。

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.