Preparation of Nanoparticles from Microemulsions Using Supercritical Antisolvent Precipitation

CBET-0827806ZareIntelligence优点：需要制备具有生物活性的纳米颗粒，并控制其形状、尺寸分布，甚至控制其周围的东西。此外，为了切合实际，这样的程序必须扩大到大量(在千克级别上，这排除了逐个原子的方法)，并且是环境友好的(绿色化学)。我们建议使用一种新技术来完成这一任务，在这种技术中，将两种不相容液体(如油和水)的微乳液作为微小液滴喷洒到第三相(超临界二氧化碳)中，第三相溶解一相，而不溶解另一相，导致不溶相析出。实际上，情况可能更加复杂，感兴趣的生物活性化合物是不可溶的，而其他两个相则溶解在超临界二氧化碳中。通过添加合适的生物相容聚合物，我们可以将我们的纳米颗粒包裹起来，以延时释放或靶向特定细胞进行摄取。利用超临界二氧化碳作为抗溶剂从微乳液中沉淀出所需的生物活性化合物是一个需要深入基础研究的课题，才能实现其可能的优势。我们已经获得了初步数据，这些数据鼓励我们相信，这种方法可以发展成一种新的药物输送方法。这项研究计划是与瑞典哥德堡查尔默斯理工大学的克里斯特·霍姆伯格教授合作完成的。他的团队在微乳液中形成无机纳米颗粒方面拥有专业知识，允许在受控的反应条件下形成5-10 nm的颗粒。我们将在超临界流体中形成和控制纳米颗粒的专业知识带到这一合作中。一个重要的新方面将是添加的包覆过程以及对颗粒的物理评价。这项工作将从纳米颗粒如何形成的基础研究，到通过研究它们在药物控制释放实验中的使用以及在活体动物中的分布来研究它们在生物系统中的行为。这两个小组的努力相辅相成，增加了这一项目成功的可能性。广泛影响：该项目的目标是开发一种新的工艺，允许形成纳米颗粒并对广泛选择的目标化合物进行封装。该工艺将产生1-5 nm范围内的颗粒，具有较窄的尺寸分布，并允许高产率地原位包覆。该过程需要较低的温度(35-45摄氏度)以及最小的加工步骤，使其与生物活性化合物兼容，并足够快地进行标记研究。拟议工艺的其他优点是减少有毒废物，并直接扩大工艺参数，以实现大批量生产的潜力。显然，这种程序的成功将对制药、微电子、食品、涂料和化妆品等其他领域产生深远影响。此外，这项研究项目将在化学、生物和工程学的交叉学科领域为一名研究生提供培训。

CBET-0827806ZareIntellectual Merit: The need exists to prepare biologically active nanoparticles with controlled shape, size distribution, and even to control what surrounds them. Moreover, to be practical, such a procedure must scale to large quantities (on the kilogram level which precludes atom-byatom approaches) and be environmentally friendly (green chemistry). We propose to accomplish this task using a new technique in which a microemulsion of two immiscible liquids (such as oil and water) is sprayed as tiny droplets into a third phase (supercritical carbon dioxide) that dissolves one phase and not the other, causing the insoluble phase to be precipitated. Actually, the situation may be yet more complex in which the biologically active compound of interest is what is insoluble whereas the other two phases dissolve in the supercritical CO2. By the addition of suitable biocompatible polymers, we can encapsulate our nanoparticles for time-delayed release or for targeting to specific cells for uptake. The use of supercritical carbon dioxide as an antisolvent for the precipitation of desired biologically active compounds from microemulsions is a subject requiring deep fundamental study before its possible advantages can be realized. We have already obtained preliminary data that encourages us to believe that this approach can be developed into a new drug delivery methodology. The research proposal is for work to be done in collaboration with Professor Krister Holmberg at Chalmers University of Technology, Gothenburg, Sweden. His group has expertise in formation of inorganic nanoparticles in microemulsions allowing 5-10 nm particles to be formed at controlled reaction conditions. We bring to this collaboration the expertise in the formation and control of nanoparticles in supercritical fluids. An important new aspect will be the added encapsulation process as well as physical evaluation of the particles. The work will range from fundamental studies of how nanoparticles are formed to how they behave in biological systems by studying their use in drug-controlled release experiments and distribution in living animals. The efforts of these two groups complement one another in a way that increases the likelihood for success of this project.Broader Impact: The goal of the project is to develop a new process which allows for nanoparticle formation and encapsulation of a wide selection of target compounds. The process will yield particles in the 1-5 nm range with a narrow size distribution as well as allow for insitu encapsulation with high yield. The process will require low temperatures (35-45 C) as well as minimal processing steps, making it compatible with bioactive compounds and rapid enough for labeling studies. Other advantages of the proposed process are reduction in toxic waste and direct scale up of the process parameters to realize the potential of achieving high-volume manufacturing. Clearly, the success of such a procedure will have profound impacts on other fields that span pharmaceuticals, microelectronics, foodstuffs, paints, and cosmetics. In addition, this research project will provide training of one graduate student in a truly interdisciplinary area at the cross section of chemistry, biology, and engineering