Micellar Separations of Poly(Ethylene Glycol)-block-Poly(Caprolactone) Nanoparticles: Subcritical and Supercritical Fluid Phase Behavior

项目摘要聚乙二醇-嵌段-聚(e-己内酯)纳米粒子的胶束分离：亚临界和超临界流体相行为Maciej Radosz/U怀俄明/CTS-0625341用于抗癌药物输送的纳米粒子是由嵌段共聚物在水溶液中形成的胶束制成的。技术挑战的例子包括如何最大限度地提高胶束核心中的药物浓度，以及如何有效地回收干胶束以供储存和运输。例如，在传统的“冷冻干燥”过程中，整个溶液被冻结，以保持胶束结构，并在真空下通过升华去除水分。这个项目是由另一种方法推动的，在这种方法中，溶剂是一种变极性的压缩流体，用于接近或低于或高于其临界温度。这种近临界流体有望更好地控制药物的传输和分配，并通过结晶从高压胶束溶液中更有效地分离胶束，而不必冻结溶剂。然而，为了探索和评估这一概念，需要一个模型两嵌段共聚物在近临界溶剂中的胶束化和结晶数据。为此，该项目旨在获取聚乙二醇、聚乙二醇酯、聚己内酯、聚己内酯及其两嵌段聚乙二醇-b-聚己内酯在亚临界和超临界流体中的可压缩溶液的实验相行为和分离数据。嵌段共聚物在这种可压缩溶液中的胶束有序-无序(ODT)转变不仅可以通过升高温度引起临界胶束温度(CMT)，还可以通过增加压力引起临界胶束压力(CMP)。CMT和CMP下形成的胶束可以通过结晶和溶剂挥发从溶液中分离出来。主要实验任务是用高压动态光散射表征聚乙二醇b-聚氯乙烯在超临界流体溶剂中的浊点分离、结晶、熔融和胶束化过程。另一项实验任务是通过冷却后的高压结晶来沉淀胶束，并通过隧道电子显微镜(TEM)表征胶束的形貌，以及它们在水中的性能与在水中制备的胶束和冻干胶束的性能进行比较。该项目的样品将被定制合成，并在另一个更大的项目中进行表征，该项目旨在为卵巢癌药物输送快速释放纳米颗粒。软材料实验室(SML)为这项工作提供了初始样品、实验室空间和设备。更广泛的影响是，这项研究将有助于探索一种新的胶束分离技术，以生产抗癌药物输送所需的纳米颗粒。该项目还将帮助培养两名博士生(一名预计将于2008年毕业)，并培训两名本科生表征导致纳米结构材料的自组装分子。

Project AbstractMicellar Separations of Poly(Ethylene Glycol)-block-Poly(e-Caprolactone) Nanoparticles:Subcritical and Supercritical Fluid Phase BehaviorMaciej Radosz / U. Wyoming / CTS-0625341Nanoparticles used for cancer drug delivery are made of micelles formed by blocky copolymers in aqueous solutions. Examples of technical challenges are how to maximize the drug concentration in the micelle core and how to recover dry micelles efficiently for storage and shipping. In a conventional 'freeze-dry' process, for example, the whole solution is frozen to preserve the micelle structure and to remove water by sublimation under vacuum. This project is motivated by an alternative approach where, instead of water, the solvent is a compressed fluid of variable polarity used near, either below or above, its critical temperature. Such a near critical fluid is expected to result in a better control of the drug transport and partitioning, and a more effective micelle separation via crystallization from the high-pressure micellar solution, without having to freeze the solvent. However, in order to explore and evaluate this concept, micellization and crystallization data are needed for a model diblock copolymer in near critical solvents. Toward this end, the project is proposed aimed at taking experimental phase behavior and separation data for compressible solutions of poly(ethylene glycol), PEG, poly(e- caprolactone), PCL, and their diblock, PEG-b-PCL, in subcritical and supercritical fluids, such as chlorodifluoromethane. The micellar order-disorder (ODT) transitions of block copolymers in such compressible solutions can be induced not only by increasing temperature, which leads to critical micelle temperature (CMT), but also by increasing pressure, which leads to critical micelle pressure (CMP). The micelles formed below CMT and CMP can be separated from solution by crystallization and solvent evaporation. The major experimental task is to characterize the cloud-point separation, crystallization, melting, and micellization of PEG-b-PCL in supercritical fluid solvents using high-pressure dynamic light scattering. Another experimental task is to precipitate the micelles by high-pressure crystallization upon cooling and to characterize their morphology through Tunneling Electron Microscopy (TEM), and their properties in water compared with those prepared in water and freeze-dried. Samples for the project will be custom synthesized and characterized in a separate larger project aimed at rapid-release nanoparticles for ovarian cancer drug delivery. Initial samples, lab space and equipment are available for this work in the Soft Materials Laboratory (SML).Broader Impact The research will enable exploring a new micelle separationtechnology for producing nanoparticles needed for cancer drug delivery. This project will also help educate two doctoral students (one expected to graduate in 2008) and train two undergraduate students in characterizing self assembling molecules that lead to nanostructured materials.