Lee Jimin, Sah Hongkee
College of Pharmacy, Ewha Womans University, 52 Ewhayeodaegil, Seodaemun-gu, Seoul 03760, Korea.
Pharmaceutics. 2022 Jul 24;14(8):1540. doi: 10.3390/pharmaceutics14081540.
Currently, emulsification-templated nanoencapsulation techniques (e.g., nanoprecipitation) have been most frequently used to prepare poly-,-lactide--glycolide (PLGA) nanoparticles. This study aimed to explore a new top-down process to produce PLGA nanoparticles. The fundamental strategy was to prepare spongelike PLGA microspheres with a highly porous texture and then crush them into submicron-sized particles via wet milling. Therefore, an ethyl formate-based ammonolysis method was developed to encapsulate progesterone into porous PLGA microspheres. Compared to a conventional solvent evaporation process, the ammonolysis technique helped reduce the tendency of drug crystallization and improved drug encapsulation efficiency accordingly (solvent evaporation, 27.6 ± 4.6%; ammonolysis, 65.1 ± 1.7%). Wet milling was performed on the highly porous microspheres with a D of 64.8 μm under various milling conditions. The size of the grinding medium was the most crucial factor for our wet milling. Milling using smaller zirconium oxide beads (0.3~1 mm) was simply ineffective. However, when larger beads with diameters of 3 and 5 mm were used, our porous microspheres were ground into submicron-sized particles. The quality of the resultant PLGA nanoparticles was demonstrated by size distribution measurement and field emission scanning electron microscopy. The present top-down process that contrasts with conventional bottom-up approaches might find application in manufacturing drug-loaded PLGA nanoparticles.
目前，乳化模板纳米包封技术（如纳米沉淀法）已最常用于制备聚丙交酯-乙交酯（PLGA）纳米颗粒。本研究旨在探索一种新的自上而下的方法来生产PLGA纳米颗粒。基本策略是制备具有高度多孔结构的海绵状PLGA微球，然后通过湿磨将其粉碎成亚微米级颗粒。因此，开发了一种基于甲酸乙酯的氨解方法，将黄体酮包封到多孔PLGA微球中。与传统的溶剂蒸发法相比，氨解技术有助于降低药物结晶的趋势，并相应提高药物包封效率（溶剂蒸发法，27.6±4.6%；氨解，65.1±1.7%）。在各种研磨条件下，对平均直径为64.8μm的高度多孔微球进行湿磨。研磨介质的尺寸是我们湿磨的最关键因素。使用较小的氧化锆珠（0.3~1mm）进行研磨根本无效。然而，当使用直径为3mm和5mm的较大珠子时，我们的多孔微球被研磨成亚微米级颗粒。通过尺寸分布测量和场发射扫描电子显微镜对所得PLGA纳米颗粒的质量进行了表征。与传统的自下而上方法形成对比的当前自上而下方法可能会在载药PLGA纳米颗粒的制造中找到应用。
