RUI: Role of Crystallinity and Morphology in Degradation and Drug Release of PEO-b-PCL Films

非技术：添加剂是塑料工程有利性能的关键组成部分。一个例子是治疗性医学治疗，它依赖于以受控方式输送药物的能力。了解添加剂和聚合物分子之间的相互作用，对于模拟分子如何从最终产品中浸出或释放是至关重要的。影响添加剂释放率的因素包括它们在聚合物分子中的分布方式、聚合物分子的排列方式以及聚合物的分解方式。本研究旨在确定这些相互作用如何影响双组分聚合物聚（环氧乙烷）-聚（己内酯）（PEO-b-PCL）的释放和降解行为。PEO-b-PCL有两种不同的成分：一种是亲水的，即水溶性的，另一种是疏水的，即不溶于水的。此外，这两种成分都可以以结晶相（结构紧凑）或无定形相（更随机和宽敞的分子排列）的形式组装。由于聚合物的二元性，添加剂可能会分散到材料的不同部分。使用不同疏水性的普通药物分子，将监测PEO和PCL结晶度，以确定添加剂对晶体形成的影响。无论添加剂是作为单个分子（分散性好）还是作为大晶体结构（分散性差）存在于聚合物中，以及它是部分地、主要地还是完全地分离成PEO或PCL，都可以观察到结晶度或晶体尺寸的降低。将改变添加剂-聚合物混合物的制备，以观察聚合物晶体结构的变化如何影响添加剂的组装。晶体结构的变化不仅会影响添加剂的释放，还会影响塑料在水中的侵蚀和降解。为了正确理解聚合物物理结构在添加剂释放和聚合物随时间分解过程中的作用，需要对结构-性能关系进行全面的分析。除了科学发现之外，这项研究还为本科生（我们未来的科学家和工程师）提供培训和发展，并促进所有人参与STEM。拓展活动包括接待一名当地高中生作为研究助理，参与K-6社区拓展计划，将学生带到校园进行工程活动，也包括在这个项目中。技术：药物控制释放依赖于药物分子和聚合物载体之间的化学或物理结构和相互作用。药物的分子分散和药物、聚合物和水之间复杂的相互作用是影响释放速度和控制的主要因素。影响药物和水分子扩散的一个潜在因素是聚合物的物理结构，其中晶体片层提供了物理屏障，微相分离提供了小分子的不均匀分散。两亲性聚环氧乙烷-嵌段聚己内酯（PEO-b-PCL）是一种具有分层物理结构的模式共聚物，包括两嵌段的结晶和随后的相分离。这些结构受到制备技术和小分子添加剂的影响。光谱和热分析技术将用于评估聚合物和药物的结构，使用不同的制备方法，热处理，药物负载和药物疏水性。PEO和PCL结构域应表现出晶体大小和/或结晶度的变化，因为它与药物的结构和分散（分子或结晶固体）以及每个结构域的分配有关。更多的疏水分子有望分离到PCL结构域；然而，装配过程中的相互作用可能更为复杂。先前确定的从边沿球晶到平面结构的晶体形态裁剪技术将用于评估存在药物添加剂或水环境下的晶体稳定性。相反，PEO晶体对PEO结构域中水的吸收会受到影响。类似的技术将用于监测水在薄膜中的扩散和随后不同亚稳性的PEO晶体的溶解。色谱和重量分析中的互补实验程序将用于测量控制释放和降解概况，以深入了解聚合物的物理结构在宏观性能中的作用。了解PEO和PCL晶体大小、结晶度和形态之间的相互作用以及由此产生的吸水、降解和药物释放特性对控制递送非常重要。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL:Additives are a crucial component in engineering advantageous properties in plastics. One example is in therapeutic medical treatments, which rely on the ability to deliver drugs in a controlled way. Understanding the interactions between additives and polymer molecules,is critical for modeling how the molecules might leach or release from the final product. Factors that contribute to the additive’s release rate include how they are distributed among the polymer molecules, how those polymer molecules are arranged, and how the polymers break down. This research aims to determine how these interactions impact the release and degradation behavior in a two-component polymer, poly(ethylene oxide)-poly(caprolactone) (PEO-b-PCL). PEO-b-PCL has two differing components: one that is hydrophilic, or water-soluble, and one that is hydrophobic, or water-insoluble. Additionally, both components can assemble in crystalline phases (having tightly structured arrangements) or amorphous phases (more random and spacious molecular arrangements). Because of the duality of the polymer, additives may partition into different sections of the material. Using common drug molecules of varying hydrophobicity, PEO and PCL crystallinity will be monitored to determine the impact of additives on crystal formation. A decrease in crystallinity or crystal size could be observed whether the additive exists in the polymer as individual molecules (good dispersion) or as large crystalline structures (poor dispersion) and whether it segregates into PEO or PCL partially, primarily, or exclusively. Preparation of the additive-polymer mixture will be varied to see how changes in the polymer crystal structure impacts the additive assembly. Not only will changes in the crystalline structure impact the additive release, it will impact the plastic’s erosion and degradation in water. A comprehensive analysis of structure-property relationships is needed to appropriately understand the role of polymer physical structure in the process of additive release and polymer breakdown over time. In addition to scientific discovery, this research provides training and development for undergraduates - our future scientists and engineers - and promotes inclusion in STEM for all. Outreach activities including hosting a local high school student as a research assistant and engagement in a K-6 community outreach program that brings students to campus for engineering activities are also included in this project.TECHNICAL:Controlled drug release relies on the chemical or physical structure and interactions between drug molecules and the polymeric carrier. Molecular dispersion of the drug and complex interactions among drug, polymer, and water are primary factors that contribute to the rate of release and its control. One underlying factor that impacts the diffusion of both drug and water molecules is the physical structure of the polymer where crystalline lamellae provide physical barriers and microphase separation provides inhomogeneous dispersion of small molecules. Amphiphilic poly(ethylene oxide)-block-poly(-caprolactone) (PEO-b-PCL) is a model copolymer with hierarchical physical structures, including crystallization of both blocks and subsequent phase separation. These structures are impacted by preparation techniques and the inclusion of small molecule additives. Spectroscopic and thermal analysis techniques will be used to evaluate the polymers’ and drug’s structures using differing preparation methods, thermal treatments, drug loading, and drug hydrophobicity. PEO and PCL domains should exhibit changes in crystal size and/or crystallinity as it correlates to the drug’s structure and dispersion (molecular or crystalline solid) and partitioning in each domain. More hydrophobic molecules are expected to segregate into the PCL domain; however, interactions during the assembly process may be more complicated. Previously determined techniques for tailoring the crystal morphology from edge-on spherulites to flat-on structures will be utilized to evaluate the crystal stability in the presence of drug additives or aqueous environments. Conversely, the absorption of water in the PEO domains should be impacted by PEO crystallites. Similar techniques will be used to monitor the diffusion of water into the film and subsequent dissolution of PEO crystals of varying metastability. Complimentary experimental procedures in chromatography and gravimetric analysis will be used to measure controlled release and degradation profiles to gain insight into the role of the polymer’s physical structure in the macroscopic properties. Understanding the interplay between the PEO and PCL crystal size, crystallinity, and morphology and resultant water absorption, degradation, and drug release properties is important for controlled delivery. .This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.