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。用于癌症药物递送的纳米粒子是由嵌段共聚物在水溶液中形成胶束制成的。技术挑战的例子是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燥的胶束用于储存和运输。例如，在传统的“冻干”过程中，整个溶液被冷冻以保持胶束结构，并在真空下通过升华去除水分。该项目的动力来自另一种替代方法，即溶剂是一种可变极性的压缩流体，在其临界温度附近（低于或高于）使用，而不是水。这种接近临界的流体有望更好地控制药物的运输和分配，并在不冻结溶剂的情况下通过高压胶束溶液的结晶更有效地分离胶束。然而，为了探索和评估这一概念，需要在接近临界溶剂中的模型二嵌段共聚物的胶束化和结晶化数据。为此，提出了该项目，旨在对亚临界和超临界流体（如氯二氟甲烷）中聚乙二醇、聚乙二醇、聚e-己内酯、PCL及其二嵌段PEG-b-PCL的可压缩溶液进行实验相行为和分离数据。在这种可压缩溶液中，嵌段共聚物的胶束有序-无序（ODT）转变不仅可以通过温度升高引起临界胶束温度（CMT），也可以通过压力升高引起临界胶束压力（CMP）。在CMT和CMP下面形成的胶束可以通过结晶和溶剂蒸发从溶液中分离出来。主要的实验任务是利用高压动态光散射表征PEG-b-PCL在超临界流体溶剂中的云点分离、结晶、熔化和胶束化。另一个实验任务是在冷却时通过高压结晶沉淀胶束，并通过隧道电子显微镜（TEM）表征其形态，并将其在水中与在水中和冷冻干燥中制备的胶束进行比较。该项目的样品将在一个单独的大型项目中进行定制合成和表征，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）提供了用于这项工作的初始样品、实验室空间和设备。这项研究将有助于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。该项目还将帮助培养两名博士生（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.