Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles
Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles
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DOI：
10.1016/j.jddst.2018.12.009
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发表时间：
2019-02-01
影响因子：
5
通讯作者：
Goepferich, Achim M.
中科院分区：
文献类型：
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作者：
Abstiens, Kathrin;Goepferich, Achim M.
在制造多组分聚合物胶体中的一个关键挑战是获得具有可再现特性的单分散纳米颗粒（NP）。本文中，通过本体纳米沉淀或微流体合成制备具有不同核壳比的NP制剂，并评估其尺寸和多分散性。微流体工艺参数，如水相和有机聚合物溶液的总流速（TFR）和流速比（FRR），被改变以调节颗粒尺寸并进一步改善尺寸分布。一般而言，本体纳米沉淀导致形成具有宽尺寸分布的较大颗粒（52-65 nm），而当用微流体系统制造时，颗粒的尺寸显著较小（24-43 nm）并且显示出相当单分散的尺寸分布。FRR被认为是改善具有高PLA-PEG与PLGA比率的NP的尺寸分布的关键因素，而它对具有较低共聚物比率的制剂的颗粒特性仅具有较小的影响。通过微流体制造成功地改善了不同NP制剂的多分散性，表明该技术是一种有价值的工具，其允许具有精确可调质量属性的多组分NP的可再现和可扩展的制造。
A key challenge in manufacturing of multicomponent polymeric colloids is obtaining monodisperse nanoparticles (NPs) with reproducible characteristics. Herein, NP formulations with varying core to shell ratios were either prepared by bulk nanoprecipitation or microfluidic synthesis and evaluated regarding their size and polydispersity. Microfluidic process parameters, such as the total flow rate (TFR) and the flow rate ratio (FRR) of the aqueous phase and the organic polymer solution, were varied to tune particle size and further improve size distribution. In general, bulk nanoprecipitation resulted in formation of larger particles (52-65 nm) with a wide size distribution, whereas particles were significantly smaller in size (24-43 nm) and displayed a rather monodisperse size distribution when they were manufactured with a microfluidic system. The FRR was identified to be the key factor for improving the size distribution of NPs with a high ratio of PLA-PEG to PLGA, whereas it had only minor impact on particle characteristics of formulations with a lower copolymer ratio. Polydispersity of different NP formulations was successfully improved by microfluidic manufacturing, demonstrating that this technology is a valuable tool that allows for reproducible and scalable manufacturing of multicomponent NPs with precisely tunable quality attributes.