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Preparation of PLGA Nanoparticles by Milling Spongelike PLGA Microspheres

초록/요약

Currently, emulsification-templated nanoencapsulation techniques (e.g., nanoprecipitation) have been most frequently used to prepare poly-d,l-lactide-co-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-50 of 64.8 mu m 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 similar to 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.

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