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

非技术性：添加剂是塑料中具有工程优势的关键成分。一个例子是治疗性医疗，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至关重要。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，或水溶性的，另一种是疏水的，或不溶于水的。此外，这两个组分都可以以晶相(具有紧密结构的排列)或非晶相(更随机和更大空间的分子排列)组装。由于聚合物的两面性，添加剂可能会分配到材料的不同部分。使用不同疏水性的常见药物分子，将监测PEO和PCL的结晶度，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)还是大晶体结构(分散性差)存在于聚合物中，以及它是否部分地、主要地或完全地分离到PEO或PCL中，都可以观察到结晶度或晶体尺寸的降低。添加剂-聚合物混合物的制备将有所不同，以了解聚合物晶体结构的变化如何影响添加剂组装。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。需要对结构-性能关系进行全面的分析，以便适当地了解聚合物物理结构在添加剂释放和聚合物随时间分解的过程中所起的作用。除了科学发现，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，并促进所有人都被纳入STEM。推广活动包括接待当地高中生作为研究助理，以及参与K-6社区推广计划，将学生带到校园进行工程活动。技术：受控药物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。药物的分子分散性和药物、聚合物和水之间的复杂相互作用是影响药物释放和控制的主要因素。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，其中晶片提供物理屏障，微相分离提供小分子的不均匀分散。两亲性聚环氧乙烷-嵌段-聚己内酯(-b-PCL)是一种具有层次化物理结构的模型共聚物，包括嵌段的结晶和随后的相分离。这些结构受到制备工艺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、药物载量和药物疏水性。PEO和PCL结构域应该表现出晶体大小和/或结晶度的变化，因为它与药物的结构和分散性(分子或晶体固体)以及在每个结构域中的分配相关。预计会有更多的疏水分子分离到PCL结构域；然而，组装过程中的相互作用可能会更加复杂。以前确定的从边向球晶到平面结构的晶体形态裁剪技术将被用来评估在药物添加剂或水环境中存在的晶体稳定性。反之，PEO微晶会影响PEO微区对水的吸收。类似的技术将被用来监测水在薄膜中的扩散以及随后不同亚稳的PEO晶体的溶解。将使用层析和重量分析中的补充实验程序来测量受控释放和降解曲线，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的晶体尺寸、结晶度和形态以及由此产生的吸水性、降解性和药物释放性能之间的相互作用对于控制给药非常重要。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.