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

CBET-0828472Radosz近临界溶剂是在临界温度以下或以上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有足够的选择性，它将产生近临界溶液，在这种溶液中，不仅可以通过降低温度来形成胶束，从而导致胶束温度，还可以通过降低压力来形成胶束，从而导致胶束压力。拟议研究的目标是了解由不同极化率或极性或两者兼而有之的嵌段组成的模型共聚物的胶束和本体相变，例如在选择性近临界溶剂中，均一且表征良好的材料的苯乙烯-嵌段-二烯和药物输送材料的例子-聚乙二醇嵌段-聚己内酯。这对于理解和开发压力敏感的胶束作用至关重要，这种胶束作用可以导致新型药物和基因传递纳米颗粒的产生。这种胶束化过程快速且可重复性，因为聚合物溶液在近临界溶剂中具有低粘度和高扩散速率。这种工艺产生的胶束不仅容易从近临界溶剂中分离出来，而且在回收和随后在水溶液配方中溶解时也可靠地保持其结构。拟议的实验任务围绕着表征模型嵌段共聚物样品的主体浊点、结晶、熔融和胶束相变展开。体相和胶束相变将由高压动态光散射确定。这项工作将有助于理解药物和杂质在可压缩胶束体系中的分配，从而有助于改变制造独特聚合物纳米颗粒的科学和工程平台。更广泛的影响拟议的项目将使两名从事这一主题的博士生能够继续他们的项目，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施。此外，用于表征块状聚合物胶束溶液的高压动态光散射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基于胶束的新型纳米颗粒技术(正在申请专利)，通过提供基本了解如何从近临界溶剂中形成和回收干燥的载药胶束，而不必冻结溶剂，而溶剂是制造药物和基因传递纳米颗粒所必需的。

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.