In-situ observation of preparation of PLGA polymeric nanoparticles using liquid cell transmission electron microscopy

Drug delivery systems using polymeric nanoparticles have been widely studied in the field of medicine and pharmacy. However, direct imaging of preparation process of polymeric nanoparticles is challenging due to damage by radiation of incident electron beam and difficulty in reproducing of preparation process. Here, we successfully visualized dynamic preparation behavior of biodegradable poly (DL-lactide-co-glycolide) (PLGA) nanoparticles during an in-situ reaction induced by the addition of PVA solution to PLGA solution. We also observed size of PLGA nanoparticles smaller during the drying process from the liquid state. By reproducing emulsion solvent diffusion (ESD) method, we realized imaging the entire series of preparation process that have not been revealed yet. This information and techniques can contribute to design of future drug formulations. They are also useful in understanding natural property and behavior of damageable materials in the liquid.