Micellization of Block Copolymers in Dilute Near-Critical Solutions: How Model Impurities and Drugs Partition Between Micellar and Solvent Phases

近临界溶剂是在低于或高于其临界温度下使用的压缩和可压缩流体。如果这种可压缩流体对形成嵌段共聚物的嵌段具有足够的选择性，那么它将导致接近临界的溶液，在这种溶液中，不仅可以通过降低温度（从而导致胶束化温度），还可以通过降低压力（从而导致胶束化压力）形成胶束。所提出的研究的目标是了解由极性或极性不同的嵌段或两者组成的模型共聚物的胶束和体相变，例如苯乙烯-嵌段二烯，一种均匀且表征良好的材料，以及聚乙二醇-嵌段聚己内酯，一种药物递送材料，两者都在选择性近临界溶剂中。这对于理解和利用压力敏感胶束化是至关重要的，它可以导致新的药物和基因递送纳米颗粒。由于聚合物溶液在接近临界的溶剂中具有低粘度和高扩散速率，因此这种胶束化过程快速且可重复。这种工艺产生的胶束不仅易于从接近临界的溶剂中分离出来，而且在回收和随后在水溶液中溶解时也能可靠地保持其结构。提出的实验任务围绕着模型嵌段共聚物样品的大块云点、结晶、熔化和胶束相变的特征而演变。体和胶束跃迁将由高压动态光散射确定。这项工作将有助于理解可压缩胶束系统中药物和杂质的分配，从而有助于改变制造独特聚合物纳米粒子的科学和工程平台。拟议的项目将使两名从事这一课题的博士生能够继续他们的项目，以表征导致纳米结构材料的自组装分子。这些学生不仅将接触到PI实验室的实验表征方法，还将接触到橡树岭国家实验室的合成和中子散射设备。此外，高压动态光散射表征块状聚合物胶束溶液的方法将被纳入研究生和本科生的热力学和聚合物科学课程。该项目还将推进一种新的基于胶束的纳米颗粒技术（专利申请中），通过提供基本的了解如何从接近临界的溶剂中形成和回收载药的干燥胶束，而无需冷冻溶剂，这对于制造药物和基因传递纳米颗粒至关重要。

CBET-0828472RadoszNear-critical solvents are compressed and compressible fluids used either below or above their critical temperatures. If such a compressible fluid is selective enough with respect to the blocks that form a block copolymer, it will lead to near-critical solution in which micelles can be formed not only by decreasing temperature, which leads to micellization temperature, but also by decreasing pressure, which leads to micellization pressure. The goal of the proposed research is to understand the micellar and bulk phase transitions of model copolymers composed of blocks that differ in polarizability or polarity or both, such as styrene-block-diene, an example of a uniform and well-characterized material, and polyethylene glycol-block-polycaprolactone, an example of a drug-delivery material, both in selective near-critical solvents. This is crucial to understand and exploit the pressure-sensitive micellization that can lead to novel drug- and gene-delivery nanoparticles. Such micellization processes are fast and reproducible because polymer solutions in near-critical solvents have low viscosity and high diffusion rates. The micelles produced from such processes are not only easy to separate from the near-critical solvent, but also reliably retain their structure upon recovery and subsequent dissolution in aqueous formulations. The proposed experimental tasks evolve around characterizing the bulk cloud-point, crystallization, melting, and micellar phase transitions of the model block copolymer samples. The bulk and micellar transitions will be determined from high-pressure dynamic light scattering. This work will help understand drug and impurity partitioning in compressible micellar systems, and hence help transform the science and engineering platform for making unique polymeric nanoparticles. Broader Impact The proposed project will enable two doctoral students working on this subject to continue their projects on characterizing self assembling molecules that lead to nanostructured materials. These students will not only be exposed to the experimental characterization methods in the PI's lab, but also to the synthesis and neutron scattering facilities at the Oak Ridge National Laboratory. Furthermore, the high-pressure dynamic light scattering method of characterizing micellar solutions of blocky polymers will be incorporated in the graduate and undergraduate thermodynamics and polymer science classes. This project will also advance a novel micelle-based nanoparticle technology (patent pending) by providing basic understanding how to form and recover dry drug-loaded micelles from near-critical solvents, without having to freeze the solvent, which is essential to manufacturing drug and gene delivery nanoparticles.