CAREER: Osmolyte-guided nanoparticle transport for effective drug/gene delivery across the mucosal barriers

职业：渗透剂引导的纳米颗粒运输，用于跨粘膜屏障的有效药物/基因递送

• 批准号: 1056997
• 负责人: Yoon Yeo
• 金额: $ 46.44万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1056997&HistoricalAwards=false
• 关键词: CAREER; Osmolyte; guided; nanoparticle; transport

This Career award by the Biomaterials program in the Division of Materials Research to Purdue University is to study mucus materials with abnormal rheological properties that significantly interfere with effective transport of nanoparticles. This project is to develop a new drug delivery strategy utilizing osmotic agents to overcome the mucus barrier. The underlying hypothesis of this project is that osmolytic agents will induce local influx of water in mucus materials to generate two favorable effects for nanoparticle diffusion: (1) induce collapse of neighboring biopolymer network, thereby increasing the spacing in the polymer mesh; and (2) decrease the viscosity of liquid in microscopic domains within the network. This project will use microscopic techniques to compare various osmolytic agents for the effect on transmucosal nanoparticle diffusion, design formulations that integrate effective osmolytic agents and nanoparticle, and evaluate the effectiveness of the osmolyte formulations using a chronic lung infection model. The outcome of this study will enhance understanding of mucus materials as a physiological barrier to drug delivery and would provide a reasonable strategy to improve treatment of diseases suffering from the mucus barrier. The proposed research will contribute to the education of next generation materials scientists, by training students in cutting-edge experimental techniques and working knowledge in the related fields. In addition, the PI will create an undergraduate class that develops training materials for K-12 students in collaboration with the Purdue Engineering Projects in Community Service.Delivering nanoparticulate therapeutics to tissues covered by abnormally thickened mucus is challenging because the mucus materials behave as a physical and chemical trap of particles and thus interfere with effective therapy in cystic fibrosis, chronic lung diseases or other related ones. The proposed project will introduce osmolytic agents in the formulation to enhance the nanoparticles penetration into the mucus materials. The underlying hypothesis is that an effective osmolytic agent will cause influx of water into the mucus and, thus, create pores that are easier for nanoparticles to travel through. This project will compare various osmotic agents for the ability to influence mucus, design and produce pharmaceutical formulations combining nanoparticles and the osmotic agents, and evaluate the effectiveness of this strategy using an animal model with chronic lung infection. The outcome of this study will enhance understanding of mucus as a physiological barrier to drug delivery, and would provide a reasonable strategy to improve treatment of diseases suffering from the mucus barrier. The proposed research will contribute to the education of next generation biomaterial scientists and engineers, by training students in cutting-edge experimental techniques and providing them with hand-on experiences. In collaboration with the Purdue Engineering Projects in Community Service, the project will create an educational program that engages K-12 and undergraduate students to stimulate public interest in science and technology.

该奖项由普渡大学材料研究部生物材料项目颁发，旨在研究具有异常流变特性的黏液材料，这些材料会显著干扰纳米颗粒的有效运输。本项目旨在开发一种利用渗透剂克服黏液屏障的新给药策略。本项目的基本假设是，渗透剂会诱导黏液材料中的局部水流入，从而对纳米颗粒的扩散产生两种有利影响：(1)诱导邻近生物聚合物网络的崩溃，从而增加聚合物网络的间距；(2)降低了网络内微观区域液体的粘度。本项目将使用显微技术来比较各种渗透剂对跨粘膜纳米颗粒扩散的影响，设计有效渗透剂和纳米颗粒相结合的配方，并使用慢性肺部感染模型评估渗透剂配方的有效性。本研究结果将增强对黏液物质作为药物传递生理屏障的认识，并为改善黏液屏障疾病的治疗提供合理的策略。通过培养学生在相关领域的前沿实验技术和工作知识，该研究将有助于下一代材料科学家的教育。此外，PI将创建一个本科班，与普渡大学社区服务工程项目合作，为K-12学生开发培训材料。将纳米颗粒治疗药物输送到被异常增厚的粘液覆盖的组织是具有挑战性的，因为粘液材料的行为就像粒子的物理和化学陷阱，从而干扰囊性纤维化、慢性肺部疾病或其他相关疾病的有效治疗。建议项目将在配方中加入渗透剂，以增强纳米颗粒对黏液材料的渗透。潜在的假设是，一种有效的渗透剂会导致水涌入粘液，从而产生更容易让纳米颗粒通过的孔。该项目将比较各种渗透剂影响粘液的能力，设计和生产结合纳米颗粒和渗透剂的药物配方，并使用慢性肺部感染的动物模型评估这一策略的有效性。本研究的结果将增强对黏液作为药物传递生理屏障的认识，并将为改善黏液屏障疾病的治疗提供合理的策略。拟议的研究将有助于下一代生物材料科学家和工程师的教育，通过培训学生尖端的实验技术，并为他们提供实践经验。与普渡大学社区服务工程项目合作，该项目将创建一个教育计划，吸引K-12和本科生，以激发公众对科学和技术的兴趣。