Integrated Production and Surface Modification of Biodegradable Nanoparticles by MEMS-Electrosprays for Drug Delivery

用于药物输送的 MEMS 电喷雾集成生产和表面修饰生物可降解纳米颗粒

• 批准号: 0907368
• 负责人: Alessandro Gomez
• 金额: $ 38.7万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0907368&HistoricalAwards=false
• 关键词: Integrated; Production; Surface; Modification; Biodegradable

ID: MPS/DMR/BMAT(7623) 0907368 PI: Gomez, Alessandro ORG: Yale UniversityTitle: Integrated Production and Surface Modification of Biodegradable Nanoparticles by MEMS-Electrosprays for Drug DeliveryThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: Surface modification of drug-loaded biodegradable nanoparticles is a prerequisite for attachment of specific ligands of interest for targeted drug delivery or for attachment of protective molecules that shield the particles during in vivo transit. The PI?s laboratory has pioneered electrospray drying methods for the production of uniform nanoparticles of biologically active agents and polymers. It is now possible to generate thousands of parallel electrosprays using microfabrication, with a packing density as large as 10,000 electroprays per square centimeter. As a result the controlled synthesis of nanoparticles at acceptable flow rates for applications is now feasible. The co-PI?s laboratory is focused on surface modification of these materials and their application to enable targeted drug and protein delivery as therapeutics for cancer and autoimmune disease. Here the combination of expertise will be focused on the development and testing of novel drug-loaded, ligand-coated nanoparticulate formulation for long-circulating, nanoparticle drug delivery. The proposed work aims to demonstrate a new fabrication process for the construction of uniformly coated drug delivery vehicles using twin-fluid, multiplexed electrosprays. Specifically, the PIs propose to demonstrate: (1) the production of uniform nanoparticles by an electrospray drying method with the overall size of 100-200 nm to facilitate cellular internalization; (2) control over drug loading and incorporation of high density coatings of targeting ligands by a twin-fluid electrospray; (3) high production rates of this formulation by parallelizing thousands of electrosprays by microfabrication; and (4) the efficacy of this novel synthesis methodology both in vitro and in vivo. Because the strength of the approach lies in a novel fabrication scheme for coating and high throughput production of drug-loaded nanoparticles, this approach lends itself to wide use in many basic and preclinical settings requiring a reproducible, robust technique for the synthesis of surface-modified drug delivery vehicles.BROADER IMPACTS: The two PIs are committed to graduate and undergraduate education, and will use this research project as a forum for advanced interdisciplinary training of students. The successful completion of the proposed research would open up huge opportunities in areas that can benefit from the unique advantage of the ES, namely, the ability to produce uniform droplets/particles over a wide range of sizes, including nanometric dimensions. Potential applications range from the controlled and/or targeted release of drugs, to the synthesis of ceramic nanoparticles, quantum dots and thin films. Results will be disseminated by the PI and his collaborators at technical meetings and in peer-reviewed articles. In addition to the anticipated impact of the proposed research in a broad range of technologies, there will be a spillover in teaching and outreach activities. The PI has been working with New Haven School teachers, as a seminar leader in the Yale-New Haven Teachers Institute (YNHTI). He gave a series of lectures on ?Energy, Engines and the Environment,? on the basis of which 12 teachers developed curricular units for classes ranging from kindergarten to high school. The model of the YNHTI has been very successful and has been exported to other inner cities across the country, as documented in http://www.yale.edu/ynhti/. He has pursued a variety of new educational initiative at the undergraduate level and has expanded his current program to involved 5 undergraduate science and engineering students in various research projects. In addition, the PIs intend to broaden this experience by organizing a 10-week Summer Outreach Program for undergraduate students entering their senior year. The program will bring together undergraduates from various institutions to participate in specific research projects covering the range of interests of the PIs.

ID：MPS/DMR/BMAT(7623)0907368 PI：Gomez，Alessandro ORG：Yale University题目：通过MEMS-电喷雾进行生物可降解纳米颗粒的集成生产和表面修饰-用于药物输送该奖项由2009年美国复苏和再投资法案(公共法律第111-5号)资助。S实验室开创了电喷雾干燥方法，用于生产均匀的生物活性物质和聚合物纳米颗粒。现在，使用微制造技术可以产生数千个平行的电喷雾，堆积密度高达每平方厘米10,000个电喷雾。因此，以可接受的流速控制合成纳米颗粒应用现在是可行的。皮？S联合实验室专注于这些材料的表面修饰及其应用，以实现靶向药物和蛋白质输送，作为癌症和自身免疫性疾病的治疗药物。在这里，专业知识的结合将集中在新型载药、配体包衣纳米颗粒制剂的开发和测试上，用于长期循环的纳米颗粒药物输送。这项拟议的工作旨在展示一种新的制造工艺，用于建造使用双流体、多路复合电喷雾的均匀涂层药物输送载体。具体地说，PI建议展示：(1)通过电喷雾干燥方法生产总尺寸为100-200 nm的均匀纳米颗粒，以促进细胞内化；(2)通过双流体电喷雾控制药物载量和加入高密度靶向配体涂层；(3)通过微细加工使数千种电喷雾并行，从而获得高生产率；以及(4)这种新的合成方法在体外和体内的有效性。由于该方法的优势在于包衣和高通量生产载药纳米颗粒的新颖制造方案，该方法被广泛应用于许多基础和临床前环境中，要求合成表面修饰的药物输送载体的可重复性、健壮的技术。BROADER影响：这两个PI致力于研究生和本科教育，并将利用该研究项目作为学生高级跨学科培训的论坛。拟议研究的成功完成将在可以受益于ES的独特优势的领域创造巨大的机会，即能够生产各种尺寸的均匀液滴/颗粒，包括纳米尺寸。潜在的应用范围从药物的受控和/或靶向释放，到陶瓷纳米颗粒、量子点和薄膜的合成。结果将由国际和平协会及其合作者在技术会议和同行评议的文章中传播。除了在广泛的技术领域进行拟议研究的预期影响外，还将对教学和外联活动产生溢出效应。作为耶鲁-纽黑文师范学院(YNHTI)的研讨会负责人，PI一直与纽黑文学校的教师合作。他发表了一系列关于能源、发动机和环境的演讲。在此基础上，12名教师制定了从幼儿园到高中的课程单元。正如http://www.yale.edu/ynhti/.所记录的那样，YNHTI的模式非常成功，并已出口到全国其他内陆城市他在本科层面推行了各种新的教育举措，并将目前的计划扩大到让5名理工科本科生参与各种研究项目。此外，PIS打算通过为进入大四的本科生组织为期10周的暑期外展计划来扩大这一经验。该计划将汇集来自不同院校的本科生，参与涵盖私人投资机构兴趣范围的具体研究项目。