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: 9085108
• 负责人: Tejal A. Desai
• 金额: $ 34.97万
• 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/9085108
• 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; 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; peptide drug; 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）：上皮屏障在20-150 kDa的尺寸范围内提供大分子的巨大障碍。特别是，将相邻细胞连接并阻塞细胞细胞空间的紧密连接络合物为大分子传递带来了重要的障碍。为了改善大分子生物制剂在遍布上皮的运输，需要开发出新的方法，以通过专门和可逆地调节紧密连接来增强细胞细胞药物的运输。在此提案中，我们研究了纳米结构表面对体外紧密连接渗透性和关键治疗分子的转运的影响。我们试图确定纳米形态增强上皮渗透性的机制，并优化纳米结构材料，以扩大可抛孢子的药物的类型。预计这些研究中获得的基本知识将增强新的上皮药物输送系统的发展。