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

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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.