Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsificationevaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsificationevaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility.

Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering).

Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between - 30 and +30 mV), with relatively narrow polydispersity.

Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.

背景：基于聚 (d,l-丙交酯-共-乙交酯) (PLGA) 的可生物降解纳米颗粒对于控释药物递送系统的开发和其他生物医学应用具有重要意义。据报道，PLGA聚合物可以通过多种技术转化为胶体纳米颗粒体系，如乳化-扩散、乳化蒸发、界面沉积、盐析、透析和纳米沉淀。由于这些溶剂的低沸点和有限的水溶性，使用包括二氯甲烷和氯仿在内的水不混溶溶剂的乳化蒸发一直是合成PLGA纳米颗粒的优选方法。然而，我们和其他人发现，当使用与水不混溶的溶剂合成 PLGA 纳米粒子时，粒子聚集，不均匀的粒度和多峰粒度分布是经常遇到的问题。这表明使用与水不混溶的溶剂合成 PLGA 纳米粒子对影响整体重现性的小程序变化高度敏感。

目的：本研究提出了一种简单而稳健的 PLGA 纳米粒子制备程序，其具有非常小的批次间变异性（由动态光散射确定的尺寸变异性（z 平均值）<5%）。

结果：结果表明，乳化溶剂扩散法与部分水混溶性溶剂（如乙酸乙酯）相结合，是制备具有高度可再现尺寸（50 至 400 nm）和 zeta 电位（介于- 30 和 +30 mV)，具有相对窄的多分散性。

结论：因此，用乙酸乙酯乳化扩散是一种更可靠的替代方法，可用于可重现和精细合成 PLGA 纳米粒子的几种现有程序。