Systematic Approaches to Scale-up of Biocompatible Drug Delivery Nanoparticles for High-Rate Production

该奖项的研究目标是探索系统的方法，以扩大一种新型的、坚固的脂质涂层聚合物药物递送纳米颗粒的高速生产，并了解大规模纳米颗粒制造过程的基本原理。采用的方法将是开发和利用搅拌槽反应器和多入口涡反应器，以追求大规模和高速率生产给药纳米颗粒的目标。为了更好地理解和优化纳米颗粒的制备工艺，将对间歇混合理论和连续混合理论进行研究。所有合成的纳米颗粒将通过一系列分析工具系统地表征粒径、表面电荷和形态、载药量、药物释放动力学和血清稳定性，以评估其可重复性和可扩展性。如果成功，这项研究的好处将包括在纳米粒子药物传递和纳米制造方面增加科学理解和技术发展。本研究为临床应用提供了具有治疗意义的载药纳米颗粒，从而推动了当前纳米医学研究的前沿。本研究的实验和理论结果可以推广到其他纳米级药物的高通量生产，并有助于对纳米制造的一般理解。此外，该项目将高度整合研究和教育活动。教育方面的努力包括招募代表性不足的本科生在实验室工作，招募高中生，重点是少数民族的暑期实习生进行4~8周的研究，以及为本科生和研究生开发纳米医学和纳米制造的新课程，以进一步传播研究成果。

The research objective of this award is to explore systematic methods to scale-up the high-rate production of a novel and robust lipid-coated polymeric drug delivery nanoparticle and to understand the principles underlying the large-scale nanoparticle fabrication process. The approach taken will be to develop and utilize a stirred-tank reactor and a multi-inlet vortex reactor to pursue the target large-scale and high-rate production of the drug delivery nanoparticles. Both the batch mixing theory and the continuous mixing theory will be studied for understanding and optimizing the nanoparticle fabrication process. All synthesized nanoparticles will be systematically characterized regarding particle size, surface charge and morphology, drug loading yield, drug release kinetics, and stability in serum by a series of analytical tools to evaluate their reproducibility and scalability.If successful, the benefits of this research will include both increased scientific understanding and technological developments on both nanoparticle drug delivery and nanomanufacturing. This research can push forward the frontier of current nanomedicine research by providing therapeutically relevant quantities of drug-loaded nanoparticles for possible clinical use. The experimental and theoretical findings from this study can be generalized for high-throughput production of other nanoscaled agents and can contribute to the general understandings of nanomanufacturing. Moreover, this project will highly integrate research and education activities. The educational efforts include recruitment of underrepresented undergraduate students working in the laboratory on the project, recruitment of high school students, with an emphasis on minority summer interns to perform 4~8 weeks of research, and development of new courses on nanomedicine and nanofabrication for both undergraduate and graduate students to further disseminate the findings from the research.