CAREER: Understanding Nanoprecipitation - Scalable Production of Polymeric Nanoparticles Encapsulating Hydrophobic Compounds

职业：了解纳米沉淀 - 封装疏水性化合物的聚合物纳米颗粒的规模化生产

• 批准号: 1350731
• 负责人: Ying Liu
• 金额: $ 40.02万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1350731&HistoricalAwards=false
• 关键词: CAREER; Understanding; Nanoprecipitation; Scalable; Production

This Early Faculty Career Development (CAREER) Program award provides funding to achieve a comprehensive understanding of the competitive kinetics required to reproducibly generate polymeric nanoparticles encapsulating hydrophobic drugs with optimized physicochemical properties. Polymeric nanoparticles as drug carriers can dramatically increase the solubility and bioavailability of hydrophobic compounds due to their large surface to volume ratio. The major challenge of developing polymeric nanoparticles for clinical applications is the production at larger scale while maintaining consistent nanoparticle properties. Due to the complexity of the process, purely empirical optimization is infeasible and quantitative prediction by a judicious interplay of simulations and experiments is essential. Time-resolved small-angle X-ray scattering integrated with a microfluidic device will be employed to experimentally observe nanoparticle structural evolution in situ. Computational fluid dynamics modeling together with population balance equations will be developed to numerically understand the coupling of mixing with precipitation. Iteration between modeling and experiments will lead to a fundamental understanding of how nanoparticle systems form, thus making it possible to efficiently design, optimize, and scale up nanoparticle production. If successful, a scalable method of nanoparticle production will have been developed, which will lead to rapid clinical translation of a variety of nanocarrier systems to deliver hydrophobic drugs and to detect and treat complex diseases. The experimental and numerical methods can be used as a platform to optimize conditions for dispersed multi-phase reactions in general. The state-of-the-art experimental observation of nanoparticle structural evolution with sub-second time resolution will greatly enhance our understanding of precipitation kinetics and nanoparticle production. The study will be integrated into the courses developed by the PI as well as into various educational activities targeting graduate, undergraduate, and 6-12 students in an interdisciplinary setting. The highly visual nature of the experimental and theoretical results and the societal relevance of the biomedical applications represent a natural draw for recruiting students to Science, Technology, Engineering, and Math (STEM) disciplines.

这项早期的教师职业发展（职业）计划奖提供了资金，以全面了解可重复生成的聚合物纳米颗粒所需的竞争动力学，该聚合物纳米颗粒将疏水性药物包含具有优化的物理化学特性。聚合物纳米颗粒作为药物载体可以大大提高疏水化合物的溶解度和生物利用度，这是由于其较大的表面与体积比。为临床应用开发聚合物纳米颗粒的主要挑战是在保持一致的纳米颗粒特性的同时，生产更大。由于过程的复杂性，纯粹的经验优化是不可行的，并且通过模拟和实验的明智相互作用进行定量预测至关重要。与微流体设备集成的时间分辨的小角度X射线散射将用于实验观察纳米颗粒的结构进化。将开发计算流体动力学建模以及种群平衡方程，以在数值上了解混合与沉淀的耦合。建模和实验之间的迭代将导致对纳米颗粒系统的形成方式的基本理解，从而使有效设计，优化和扩展纳米颗粒的产生成为可能。如果成功，将开发一种可扩展的纳米颗粒产生方法，这将导致各种纳米载体系统的快速临床翻译，以输送疏水性药物并检测和治疗复杂疾病。实验和数值方法可以用作平台，以优化分散多相反应的条件。对纳米颗粒结构进化的最先进的实验观察，并分辨率下时间分辨率将大大增强我们对降水动力学和纳米颗粒产生的理解。该研究将纳入PI开发的课程，以及针对跨学科的研究生，本科和6至12名学生的各种教育活动。实验结果和理论结果的高度视觉性质以及生物医学应用的社会相关性代表了招募科学，技术，工程和数学（STEM）学科的自然吸引力。