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

CBET-0828472 Radosz近临界溶剂是在其临界温度以下或以上使用的压缩和可压缩流体。如果这样的可压缩流体对于形成嵌段共聚物的嵌段具有足够的选择性，则它将导致近临界溶液，其中胶束不仅可以通过降低温度（这导致胶束化温度）而且可以通过降低压力（这导致胶束化压力）来形成。所提出的研究的目标是了解胶束和本体相变的模型共聚物组成的嵌段不同的极化率或极性或两者，如苯乙烯嵌段二烯，一个例子的一个均匀的和良好的表征材料，和聚乙二醇嵌段聚己内酯，一个例子的药物输送材料，无论是在选择性的近临界溶剂。这对于理解和利用可导致新型药物和基因递送纳米颗粒的压力敏感胶束化至关重要。这种胶束化过程是快速和可再现的，因为在近临界溶剂中的聚合物溶液具有低粘度和高扩散速率。从这样的过程中产生的胶束不仅容易从近临界溶剂中分离，而且在回收和随后溶解在水性制剂中时可靠地保持其结构。拟议的实验任务演变周围的表征散装浊点，结晶，熔融和胶束相变的模型嵌段共聚物样品。将从高压动态光散射确定本体和胶束转变。这项工作将有助于了解药物和杂质在可压缩胶束系统中的分配，从而有助于改变科学和工程平台，以制造独特的聚合物纳米颗粒。更广泛的影响拟议的项目将使两名博士生在这个问题上工作，继续他们的项目，对表征自组装分子，导致纳米结构材料。这些学生不仅将接触到PI实验室的实验表征方法，而且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，高压动态光散射方法表征胶束解决方案的块状聚合物将被纳入研究生和本科生热力学和聚合物科学类。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），通过提供基本的理解如何从近临界溶剂中形成和回收干燥的载药胶束，而不必冷冻溶剂，这对于制造药物和基因递送纳米颗粒至关重要。

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.