Rational Design of Biodegradable Polymer Particles Using Carbon Dioxide

利用二氧化碳合理设计可生物降解聚合物颗粒

• 批准号: 0553659
• 负责人: Annette Shine
• 金额: --
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0553659&HistoricalAwards=false
• 关键词: Rational; Design; Biodegradable; Polymer; Particles

National Science Foundation - Division of Chemical &Transport Systems Particulate & Multiphase Processes Program (1415)ABSTRACTProposal Number: 0553659Principal Investigator: Shine, Annette D.Affiliation: University of Delaware Proposal Title: Rational Design of Biodegradable Polymer Particles Using Carbon DioxideIntellectual MeritIn this proposed research, a rational design methodology is developed for a process to produce finebiodegradable polymeric particles suitable for pulmonary drug delivery applications. The process, termed PLUSS (Polymer Liquefaction Using Supercritical Solvation, uses compressed carbon dioxide to liquefy the polymer, followed by rapid depressurization to precipitate the polymer, free of residual solvents. In a significant departure from previous modeling, this work postulates that the morphology of precipitated polymers is governed primarily by two-phase flow hydrodynamics. The variety of experimentally observed particulate morphologies (spheres, porous irregular-shaped particles, fibers, etc.) is attributed to the solidification of the polymer in different regions of the two-phase flow map (e.g., dispersed droplet, annular, or slug flow). The PLUSS process will be examined using both experiments and process modeling. Modeling will use the assumption of homogeneous equilibrium between polymer-rich and pure CO2 phases. The objective of the modeling is to identify the structure of the phase-separated fluid at the point of polymer solidification, by mapping process conditions onto a suitable two-phase flow diagram. An experimental PLUSS apparatus will be constructed which allows independent control of the component fluxes and CO2 density, with depressurization occurring across a capillary. Particle morphology, size distribution and porosity will be determined experimentally for crystalline (polycaprolactone, polyethylene glycol) and amorphous poly(lactic-co-glycolic acid) polymers of interest in pharmaceutical applications, and comparisons made with property predictions from the two-phase PLUSS modeling. Where necessary, viscosity, melting point (or glass transition) depression and interfacial tension will be determined so that reliable model predictions can be made.If successful, this combination of experimental and modeling work will enable, for the first time, therational design of particles using supercritical CO2 processing. If the hypothesis of two-phase flow dominance isconfirmed, then innovative equipment designs are suggested, such as elbows to enhance secondary flows andpromote smaller particles. A major outcome of the project will be unifying the description of supercritical fluidparticle formation processes through the quantitative application of two-phase flow hydrodynamics.Broader Impacts Broader impacts of the project include the potential for application in drug delivery together with the development of future scientists and engineers through its training of undergraduate and graduate student researchers, and through its outreach to secondary school students and teachers. High school science teachers will perform summer research to develop an inexpensive, student-friendly version of the viscosity-measurement system that can be replicated in other classrooms. Using this equipment, students can be directly and collaboratively involved in the acquisition of research data relevant to development of a glucose monitor for diabetics, while simultaneously meeting state science curriculum standards, and having fun with

美国国家科学基金会-化学运输系统分部颗粒多相过程计划（1415）摘要提案编号：0553659主要研究员：Shine，Annette D. 特拉华州大学的提案标题：合理设计的生物降解聚合物粒子使用二氧化碳的智力MeritIn这项拟议的研究，合理的设计方法是开发的过程中，以生产fineedegradable聚合物粒子适用于肺部药物输送应用。该工艺被称为PLUSS（使用超临界溶剂化的聚合物液化），使用压缩二氧化碳将聚合物液化，然后快速减压以沉淀聚合物，不含残留溶剂。在一个显着偏离以前的建模，这项工作假设，沉淀聚合物的形态主要是由两相流流体力学。实验观察到的颗粒形态（球体、多孔不规则形状颗粒、纤维等）的多样性。归因于聚合物在两相流图的不同区域中的固化（例如，分散的液滴、环形或段塞流）。将使用实验和过程建模来检查PLUSS过程。建模将使用富聚合物和纯CO2相之间的均匀平衡的假设。建模的目的是通过将工艺条件映射到合适的两相流图上来识别聚合物固化点处的相分离流体的结构。将构建一个实验PLUSS装置，它允许独立控制的组件通量和CO2密度，与减压发生在整个毛细管。颗粒形态，尺寸分布和孔隙率将实验确定的结晶（聚己内酯，聚乙二醇）和非晶聚（乳酸-羟基乙酸）聚合物在制药应用中的利益，并与性能预测的两相PLUSS建模进行比较。必要时，将测定粘度、熔点（或玻璃化转变）降低和界面张力，以便进行可靠的模型预测。如果成功，这种实验和建模工作的结合将首次实现使用超临界CO2处理的颗粒的合理设计。如果两相流占主导地位的假设得到证实，则建议进行创新的设备设计，例如弯头以增强二次流并促进更小的颗粒。该项目的一个主要成果是通过两相流流体动力学的定量应用统一描述超临界流体颗粒形成过程。更广泛的影响该项目的更广泛的影响包括在药物输送中的应用潜力以及通过对本科生和研究生研究人员的培训培养未来的科学家和工程师，并通过向中学学生和教师推广。高中科学教师将进行夏季研究，以开发一个便宜的，学生友好的版本的粘度测量系统，可以复制在其他教室。使用该设备，学生可以直接和协作地参与获取与糖尿病患者血糖监测仪开发相关的研究数据，同时满足国家科学课程标准，并享受