Haque Shadabul, Boyd Ben J, McIntosh Michelle P, Pouton Colin W, Kaminskas Lisa M, Whittaker Michael
1Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, ParkvilleVIC, 3052, Australia; 2ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Melbourne, VIC, 3052, Australia; 3School of Biomedical Sciences, University of Queensland, St LuciaQLD, 4072, Australia.
Curr Nanosci. 2018 Oct;14(5):448-453. doi: 10.2174/1573413714666180313130235.
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, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immisci-ble 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 reproduc-ibility.
This study presents a simple and robust procedure for the preparation of PLGA nanoparti-cles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering).
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 na-noparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between -30 and +30 mV), with relatively narrow polydispersity.
Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to sev-eral existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.
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以及其他生物医学应用至关重要。据报道，PLGA聚合物可通过多种技术转化为胶体纳米颗粒系统，如乳化扩散、乳化蒸发、界面沉积、盐析、透析和纳米沉淀。由于二氯甲烷和氯仿等与水不混溶的溶剂沸点低且水溶性有限，采用这些溶剂的乳化蒸发法一直是合成PLGA纳米颗粒的首选方法。然而，我们和其他人发现，当使用与水不混溶的溶剂合成PLGA纳米颗粒时，颗粒聚集、粒径不均匀和多峰粒径分布是常见问题。这表明使用与水不混溶的溶剂合成PLGA纳米颗粒对影响整体重现性的微小操作变化高度敏感。
本研究提出了一种简单且可靠的方法来制备批次间变异性非常小的PLGA纳米颗粒（通过动态光散射测定，粒径（z-平均）的变异性<5%）。
结果表明，乳化溶剂扩散法与部分与水混溶的溶剂（如乙酸乙酯）相结合，是制备具有高度可重现粒径（50至400nm之间）和zeta电位（-30至+30mV之间）、多分散性相对较窄的PLGA纳米颗粒的通用方法。
因此，用乙酸乙酯进行乳化扩散是一种比几种现有方法更可靠的替代方法，可用于可重现且精细地合成PLGA纳米颗粒。
