Reversible pH-Driven Flocculation of Amphiphilic Polyelectrolyte-Coated Nanoparticles for Rapid Filtration and Concentration,ACS Applied Nano Materials

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Reversible pH-Driven Flocculation of Amphiphilic Polyelectrolyte-Coated Nanoparticles for Rapid Filtration and Concentration
ACS Applied Nano Materials ( IF 5.3 ) Pub Date : 2021-08-24 , DOI: 10.1021/acsanm.1c00707
Kurt D. Ristroph ₁ , Jenna A. Ott ₁ , Luqman A. Issah ₁ , Brian K. Wilson ₁ , Amila Kujović ₁ , Madeleine Armstrong ₁ , Sujit S. Datta ₁ , Robert K. Prud’homme ₁

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Nanoformulating poorly water-soluble drugs is attractive for improving oral dissolution kinetics, but concentrating and drying dilute nanoparticle (NP) suspensions is a barrier to translation. This work describes a reversible, pH-driven flocculation technique for concentrating NPs stabilized with a carboxylic acid-bearing cellulose polymer. Lumefantrine NPs 150 nm in diameter stabilized by anionic hydroxypropylmethylcellulose acetate succinate, a Food and Drug Administration-approved pharmaceutical polymer excipient, are prepared using flash nanoprecipitation. Particles are then concentrated 50-fold by acid-induced flocculation at pH 2.0, separation (either filtration or centrifugation), and base-induced redispersion at pH 6.9, reducing the drying time 50-fold. Dried powders retain enhanced lumefantrine dissolution kinetics. Filtration efficiency is assessed, and flocculation is found to improve NP retention from 3 to 85% on a 2.5 μm filter. The kinetics of flocculation and the fractal nature of the flocs are studied using confocal microscopy and agree closely with a diffusion-limited aggregation model. These results demonstrate a proof of concept that reversible flocculation is a facile method for separating amphiphilic polyelectrolyte-coated NPs from suspension for advanced processing.

中文翻译：

用于快速过滤和浓缩的两亲性聚电解质涂层纳米颗粒的可逆 pH 驱动絮凝

纳米制剂水溶性差的药物对于改善口服溶出动力学很有吸引力，但浓缩和干燥稀释的纳米颗粒 (NP) 悬浮液是转化的障碍。这项工作描述了一种可逆的、pH 驱动的絮凝技术，用于浓缩用含羧酸的纤维素聚合物稳定的 NP。使用快速纳米沉淀法制备由阴离子羟丙基甲基纤维素乙酸琥珀酸酯稳定的直径 150 nm 的 Lumefantrine NP，这是一种食品和药物管理局批准的药物聚合物赋形剂。然后通过在 pH 2.0 时酸诱导絮凝、分离（过滤或离心）和在 pH 6.9 时碱诱导再分散将颗粒浓缩 50 倍，从而将干燥时间缩短 50 倍。干粉保留增强的苯芴醇溶出动力学。评估过滤效率，发现絮凝可将 2.5 μm 过滤器上的 NP 保留率从 3% 提高到 85%。絮凝动力学和絮状物的分形性质使用共聚焦显微镜进行研究，并且与扩散限制聚集模型非常吻合。这些结果证明了可逆絮凝是一种从悬浮液中分离两亲性聚电解质涂覆的纳米颗粒以进行高级加工的简便方法的概念证明。

更新日期：2021-09-24

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