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

聚乙二醇嵌段-聚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.怀俄明州/ CTS-0625341用于癌症药物递送的纳米颗粒由水溶液中的嵌段共聚物形成的胶束制成。技术挑战的实例是如何使胶束核心中的药物浓度最大化以及如何有效地回收干燥胶束用于储存和运输。例如，在常规的“冷冻干燥”过程中，整个溶液被冷冻以保持胶束结构并通过在真空下升华来除去水。该项目的动机是一种替代方法，其中溶剂不是水，而是在其临界温度附近（低于或高于）使用的可变极性的压缩流体。预期这种近临界流体会导致药物转运和分配的更好控制，以及通过从高压胶束溶液中结晶而更有效的胶束分离，而不必冷冻溶剂。然而，为了探索和评估这一概念，胶束化和结晶的数据需要在近临界溶剂中的模型二嵌段共聚物。为此，提出了该项目，旨在采取实验相行为和分离数据的可压缩解决方案的聚（乙二醇），PEG，聚（e-己内酯），PCL，和他们的二嵌段，PEG-b-PCL，在亚临界和超临界流体，如氯二氟甲烷。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（导致临界胶束温度（CMT））来诱导，而且可以通过升高压力（导致临界胶束压力（CMP））来诱导。在CMT和CMP下形成的胶束可以通过结晶和溶剂蒸发从溶液中分离。主要的实验任务是使用高压动态光散射来表征PEG-b-PCL在超临界流体溶剂中的浊点分离、结晶、熔融和胶束化。另一个实验任务是通过冷却后的高压结晶沉淀胶束，并通过透射电子显微镜（TEM）表征其形态，并将其在水中的性质与在水中制备和冷冻干燥的性质进行比较。该项目的样品将在一个单独的更大的项目中定制合成和表征，该项目旨在为卵巢癌药物递送提供快速释放的纳米颗粒。最初的样品，实验室空间和设备可用于软材料实验室（SML）的这项工作。更广泛的影响这项研究将能够探索一种新的胶束分离技术，用于生产癌症药物输送所需的纳米颗粒。该项目还将帮助教育两名博士生（其中一名预计将于2008年毕业），并培训两名本科生描述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.