Flash precipitation of random copolymers in a micro-mixer for controlling the size and surface charge of nanoparticles

Abstract

Precisely controlling the size and surface chemistry of polymeric nanoparticles (P-NPs) is critical for their versatile engineering and biomedical applications. In this work, various NPs of amphipathic random copolymers were comparatively produced by the flash nanoprecipitation (FNP) method using a tube-in-tube type of micro-mixer up to 330 mg min⁻¹ in production scale in a kinetically controlled manner. The NPs obtained from poly(styrene-co-maleic acid), poly(styrene-co-allyl alcohol), and poly(methyl methacrylate-co-methacrylic acid) were concurrently controlled in the range 51–819 nm in size with narrow polydispersity index (<0.1) and −44 to −16 mV in zeta potential, by depending not only on the polymeric chemistry and the concentration but also the mixing behavior of good solvents (THF, alcohols) and anti-solvent (water) under three flow regimes (laminar, vortex and turbulence, turbulent jet). Moreover, the P(St-MA) derived NPs under turbulent jet flow conditions were post-treated in the initial solution mixture for up to 16 h, resulting in lowering of the zeta potential to −52 mV from the initial −27 mV and decreasing size to 46 nm from 50 nm by further migration of hydrophilic segments with –COOH groups on the outer surface, and the removal of THF trapped in the hydrophobic core.