Mechanisms of nanostructure-enhanced transepithelial drug delivery

纳米结构增强的跨上皮药物递送机制

• 批准号: 8929244
• 负责人: Tejal A. Desai
• 金额: $ 34.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-18 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8929244
• 关键词: Actins; Biological Assay; Bovine Serum Albumin; Cells; Chemicals; Co-Immunoprecipitations; Complex; Cues; Development; Dose; Drug Delivery Systems; Drug Transport; Electrical Resistance; Enhancers; Epithelial; Epithelium; Etanercept; Eye; F-Actin; Film; Focal Adhesions; Gastrointestinal tract structure; Geometry; Goals; Health; Height; Immunoglobulin G; In Vitro; Injection of therapeutic agent; Integrin Inhibition; Integrins; Intramuscular; Knowledge; Lead; Link; Mechanics; Mediating; Mediator of activation protein; Microscopy; Modeling; Molecular; Molecular Weight; Morphology; Names; Nanostructures; Nanotopography; Nose; Oral cavity; Pain; Pathway interactions; Peptides; Permeability; Pharmaceutical Preparations; Proteins; Resolution; Route; Signal Transduction; Skin; Structure; Surface; Therapeutic; Therapeutic Agents; Tight Junctions; absorption; immunocytochemistry; improved; macromolecule; molecular rearrangement; nanopattern; nanostructured; novel strategies; novel therapeutics; protein structure; response; subcutaneous

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.

描述（由申请人提供）：上皮屏障对20 - 150 kDa大小范围内的大分子的递送存在显著障碍。特别地，连接相邻细胞并阻塞细胞旁空间的紧密连接复合物对大分子的递送构成显著障碍。为了改善大分子生物制剂跨上皮的转运，需要开发通过特异性和可逆性调节紧密连接来增强细胞旁药物转运的新方法。在这个提议中，我们研究了纳米结构表面对紧密连接通透性和关键治疗分子体外转运的调节作用。我们试图确定的机制，通过它的上皮渗透性增强nanotopography和优化纳米结构的材料，以扩大类型的药物，可以提供paracellarely。预计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。