Reversible pH-Driven Flocculation of Amphiphilic Polyelectrolyte-Coated Nanoparticles for Rapid Filtration and Concentration

Abstract

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 diffusionlimited 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.

Effects of the polymer glass transition on the stability of nanoparticle dispersions

“…Electrostatic-stabilized polymer NPs represent a valuable class of colloids given their tunable interactions, chemistries, and morphologies. While the size stability of these dispersions can be correlated with formulation parameters such as particle size, salt concentration, and surface charge group density, [18][19][20][21] the effect of the underlying polymer mobility, characterized by the glass transition temperature (T g ), has not been thoroughly studied. 22,23 When preparing polymer NPs via precipitation, the T g has been shown to define vitrification timescales, allowing for complex morphologies to form from the kinetic arrest of phase separation in polymer blend NPs.…”

Flash NanoPrecipitation as an Agrochemical Nanocarrier Formulation Platform: Phloem Uptake and Translocation after Foliar Administration

“…Two recent advancements in FNP make the technology an attractive option for nanoformulating agrochemicals. The first enables the encapsulation of ionizable hydrophilic molecules, − enabling encapsulation of both hydrophobic and hydrophilic AIs, and the second replaces high-cost block copolymer stabilizers with low-cost alternatives such as lecithin, gelatin, a combination of the corn protein zein with the milk protein byproduct casein, and hydroxypropyl methylcellulose acetate succinate (HPMCAS), ,− a semisynthetic cellulose derivative used in the pharmaceutical industry. The result is a platform technology for manufacturing, at large scales and low per-unit costs, NCs capable of encapsulating a wide range of payloads.…”