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.

该早期教师职业发展（CAREER）计划奖提供资金，以实现对可重复生成聚合物纳米颗粒所需的竞争动力学的全面理解，这些聚合物纳米颗粒封装具有优化的物理化学性质的疏水药物。聚合物纳米粒作为药物载体，由于其大的表面积与体积比，可以显著提高疏水性化合物的溶解度和生物利用度。开发用于临床应用的聚合物纳米颗粒的主要挑战是在保持一致的纳米颗粒性质的同时以更大规模生产。由于该过程的复杂性，纯经验优化是不可行的，通过模拟和实验的明智相互作用进行定量预测是必不可少的。时间分辨小角X射线散射与微流控装置集成将被用来实验观察纳米粒子的结构演变原位。将发展计算流体动力学模型和人口平衡方程，以便从数值上了解混合与降水的耦合。建模和实验之间的迭代将导致对纳米颗粒系统如何形成的基本理解，从而使有效设计，优化和扩大纳米颗粒生产成为可能。如果成功，将开发出一种可扩展的纳米颗粒生产方法，这将导致各种纳米载体系统的快速临床转化，以提供疏水药物并检测和治疗复杂疾病。实验和数值方法可以作为优化分散多相反应条件的平台。以亚秒级时间分辨率对纳米颗粒结构演变进行的最先进的实验观察将大大增强我们对沉淀动力学和纳米颗粒生产的理解。该研究将被整合到PI开发的课程中，以及针对研究生，本科生和6-12名学生的跨学科教育活动中。实验和理论结果的高度可视化以及生物医学应用的社会相关性代表了招收学生到科学，技术，工程和数学（STEM）学科的自然吸引力。