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: 8748142
• 负责人: Tejal A. Desai
• 金额: $ 35.71万
• 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/8748142
• 关键词: Actins; Biological Assay; Bovine Serum Albumin; Cells; Chemicals; Co-Immunoprecipitations; Complex; Cues; DNA Sequence Rearrangement; Development; Dose; Drug Delivery Systems; Drug Transport; Electrical Resistance; Enhancers; Epithelial; Epithelium; Etanercept; Eye; F-Actin; Film; Focal Adhesions; Gastrointestinal tract structure; Geometry; Goals; 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; public health relevance; response; subcutaneous

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.

摘要