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.

抽象的 上皮屏障对大分子在细胞内的传递构成了重大障碍。 大小范围为 20 - 150 kDa。特别是，连接相邻细胞的紧密连接复合体 并闭塞细胞旁空间，对递送产生重大障碍 大分子。为了改善大分子生物制剂跨上皮细胞的运输，新的 需要开发通过特异性和增强细胞旁药物转运的方法 可逆地调节紧密连接。在本提案中，我们研究了以下效果： 纳米结构表面对紧密连接渗透性和关键传输的调节 体外治疗分子。我们试图确定上皮细胞的机制 通过纳米形貌增强渗透性并优化纳米结构材料以拓宽 可以旁细胞递送的药物类型。预计基本面 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。