GOALI: Continuous Coating of Ultrafine Drug Particles by Heterogeneous Polymer Nucleation in a Hollow Fiber Membrane Module

这项学术与工业联络资助机会（GOALI）计划为开发纳米级药物颗粒连续薄膜涂层的新方法提供资金，以生产大量具有所需生物可降解聚合物涂层层的单独涂层颗粒。涂层方法利用采用冷却结晶和/或抗溶剂结晶的中空纤维膜装置。这两种设计都可以通过非均相聚合物成核使溶解的聚合物从溶液中沉淀到悬浮中的纳米颗粒上。由二氧化硅纳米颗粒组成的模型系统将悬浮在含有溶解聚合物（如Eudragit或PLGA）的有机溶剂中。这样的溶液，有或没有其他添加剂，如表面活性剂，以防止团聚，将经受聚合物沉淀到纳米颗粒表面，形成适当的薄膜涂层。中空纤维装置应允许对模型系统的聚合物涂层进行连续处理，并将与工业合作伙伴百时美施贵宝（BMS）提供的制药相关系统一起进行测试。采用SEM、EDX和TEM-EELS等电镜技术对聚合物涂层进行表征；将建立数学模型来预测非均相成核驱动的涂层过程。聚合物涂层使药物以持续/可控的方式释放，通过减少给药频率提高药物的生物利用度和患者的依从性，允许纳米级药物颗粒克服粘液屏障并靶向特定的身体器官，并防止免疫细胞（巨噬细胞）吞噬和消除血液中的纳米级药物颗粒。如果成功，这项研究将开发出一种连续的、可扩展的纳米颗粒涂层系统，该系统可以在比依赖超临界流体的温度和压力更接近环境的条件下生产大量的聚合物涂层纳米颗粒。这种工艺应该在制药和其他工业中得到广泛应用。通过与BMS合作，这些流程将扩大规模，并探索商业化的可能性。

This Grant Opportunity for Academic Liaison with Industry (GOALI) Program award provides funding for developing a new method for continuous film coating of nano-sized drug particles to produce large amounts of individually coated particles having a desired layer of a biodegradable polymer coating. The coating method utilizes hollow fiber membrane devices employing either cooling crystallization and/or antisolvent crystallization. Both designs will enable controlled precipitation of a dissolved polymer from solution onto nanoparticles in suspension by heterogeneous polymer nucleation. A model system consisting of silica nanoparticles will be suspended in an organic solvent containing the dissolved polymer such as Eudragit or PLGA. Such a solution, with or without other additives such as surfactants to prevent agglomeration, will be subjected to polymer precipitation onto the nanoparticle surface to form an appropriate film coating. The hollow fiber devices should allow continuous processing of polymer coating of the model systems and will be tested with pharmaceutically relevant systems supplied by the industrial partner Bristol-Myers Squibb (BMS). The polymer coatings will be characterized by SEM, EDX and TEM-EELS electron microscopic techniques; mathematical models will be developed to predict the heterogeneous nucleation-driven coating processes. The polymer coating enables the drug release in a sustained/controlled manner, improves drug bioavailability and patient compliance by reducing the drug administration frequency, allows nano-sized drugs particles to overcome a mucus barrier and target specific body organs, and prevents immune cells (macrophages) from engulfing and eliminating nano-sized drug particles in the bloodstream.If successful, this research will develop a continuous, scalable, nanoparticle coating system that can produce large quantities of polymer-coated nanoparticles while operating at temperatures and pressures far closer to ambient than those relying on supercritical fluids. Such a process should find widespread application in the pharmaceutical and other industries. Working in partnership with BMS, these processes will be scaled-up and commercialization possibilities will be explored.