Beck-Broichsitter Moritz, Nicolas Julien, Couvreur Patrick
Institut Galien Paris-Sud, CNRS UMR 8612, University of Paris-Sud, F-92196, Châtenay-Malabry Cedex, France.
Nanoscale. 2015;7(20):9215-21. doi: 10.1039/c5nr01695a. Epub 2015 Apr 30.
Polymer nanoparticles (NPs) offer versatile novel biological features of interest for drug delivery applications. "Ouzo diagrams" allowed for a systematic manufacture of specified colloidal formulations by the widely used nanoprecipitation process. Surprisingly, despite the well-documented relevance of the applied organic solvent for nanoprecipitation, its effect on the actual status of the "Ouzo region" was so far not studied. Herein, investigations were undertaken to account for the potential impact of the solvent type on the "Ouzo diagrams" for poly(lactide-co-glycolide) (PLGA) and tetrahydrofuran (THF), 1,4-dioxane, acetone and dimethyl sulfoxide (DMSO). The "Ouzo region" shifted considerably to higher polymer fractions upon solvent change (rank order: THF < 1,4-dioxane < acetone < DMSO). Assuming a one-to-one transformation of detached PLGA-bearing solvent droplets (droplet diameter for THF: ∼800 nm, 1,4-dioxane: ∼700 nm, acetone: ∼500 nm and DMSO: ∼300 nm) into non-divisible polymer aggregates upon solvent displacement, facilitated to predict the size of NPs found within the "Ouzo region" (size range: 40-200 nm). In conclusion, application of "Ouzo diagrams" is a valuable tool for drug delivery research and will most-likely replace the "trial-and-error"-approach to identify the operating window for the production of stable colloidal formulations by the nanoprecipitation technique.
聚合物纳米颗粒（NPs）具有多种新颖的生物学特性，在药物递送应用中具有重要意义。“乌佐图”通过广泛使用的纳米沉淀法实现了特定胶体配方的系统制备。令人惊讶的是，尽管有机溶剂在纳米沉淀中的作用已有充分记录，但迄今为止尚未研究其对“乌佐区域”实际状态的影响。在此，我们进行了研究，以探讨溶剂类型对聚（丙交酯 - 乙交酯）（PLGA）与四氢呋喃（THF）、1,4 - 二氧六环、丙酮和二甲基亚砜（DMSO）形成的“乌佐图”的潜在影响。随着溶剂的变化，“乌佐区域”显著向更高的聚合物分数偏移（排序为：THF < 1,4 - 二氧六环 < 丙酮 < DMSO）。假设在溶剂置换后，带有PLGA的分离溶剂液滴（THF的液滴直径约为800 nm，1,4 - 二氧六环约为700 nm，丙酮约为500 nm，DMSO约为300 nm）一对一转化为不可分割的聚合物聚集体，这有助于预测在“乌佐区域”内发现的纳米颗粒的大小（尺寸范围：40 - 200 nm）。总之，“乌佐图”的应用是药物递送研究的一个有价值的工具，很可能会取代“试错”方法，以确定通过纳米沉淀技术生产稳定胶体配方的操作窗口。
