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

ID：MPS/DMR/BMAT（7623）0907368 PI：Gomez，Alessandro ORG：Yale University耶鲁大学通过MEMS-电喷雾用于药物递送的生物可降解纳米颗粒的集成生产和表面改性该奖项由2009年美国复苏和再投资法案资助（公法111-5）.知识产权：药物表面改性-负载的可生物降解的纳米颗粒是连接用于靶向药物递送的感兴趣的特异性配体或连接保护性分子的先决条件，在体内运输过程中的颗粒。 私家侦探？的实验室已经开创了电喷雾干燥方法，用于生产生物活性剂和聚合物的均匀纳米颗粒。现在可以使用微加工产生数千个平行的电喷雾，其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的应用现在是可行的。合作伙伴？该实验室专注于这些材料的表面改性及其应用，以使靶向药物和蛋白质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开发和测试新的载药，配体涂层纳米颗粒制剂的长循环，纳米颗粒药物输送。拟议的工作旨在展示一种新的制造工艺，用于使用双流体，多路复用电喷雾构建均匀涂层的药物递送载体。具体而言，PI建议证明：（1）通过电喷雾干燥方法生产总体尺寸为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载药量和掺入靶向配体的高密度涂层;（3）通过微细加工使数千个电喷雾平行化，该制剂的高生产率;和（4）这种新的合成方法在体外和体内的功效。由于该方法的优势在于用于涂覆和高通量生产载药纳米颗粒的新型制造方案，因此该方法适合于在许多基础和临床前环境中广泛使用，这些环境需要用于合成表面改性药物递送载体的可重现的稳健技术。这两个PI致力于研究生和本科教育，并将利用这个研究项目作为学生先进的跨学科培训的论坛。拟议研究的成功完成将为能够受益于ES独特优势的领域开辟巨大的机会，即能够在包括纳米尺寸在内的各种尺寸范围内产生均匀的液滴/颗粒。潜在的应用范围从药物的控制和/或靶向释放，到陶瓷纳米颗粒，量子点和薄膜的合成。PI及其合作者将在技术会议和同行评审文章中传播结果。除了拟议的研究在广泛的技术领域产生的预期影响外，还将在教学和外联活动方面产生溢出效应。 PI一直与纽黑文学校教师合作，作为耶鲁纽黑文教师研究所（YNHTI）的研讨会领导者。他做了一系列的讲座？能源、发动机与环境在此基础上，12名教师为从幼儿园到高中的各个班级制定了课程单元。YNHTI的模式非常成功，并已出口到全国其他城市，如http://www.yale.edu/ynhti/所述。他在本科阶段推行了各种新的教育计划，并扩大了他目前的计划，使5名本科理工科学生参与了各种研究项目。此外，PI打算通过为进入高年级的本科生组织为期10周的夏季外展计划来扩大这种经验。该计划将汇集来自不同机构的本科生参加涵盖PI兴趣范围的具体研究项目。

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.