Solvent Controls Nanoparticle Size during Nanoprecipitation by Limiting Block Copolymer Assembly

Abstract

Control of the properties of nanoparticles (NPs), including size, is critical for their application in biomedicine and engineering. Polymeric NPs are commonly produced by nanoprecipitation, where a solvent containing a block copolymer is mixed rapidly with a nonsolvent, such as water. Empirical evidence suggests that the choice of solvent influences NP size; yet, the specific mechanism remains unclear. Here, we show that solvent controls NP size by limiting block copolymer assembly. In the initial stages of mixing, polymers assemble into dynamic aggregates that grow via polymer exchange. At later stages of mixing, further growth is prevented beyond a solvent-specific water fraction. Thus, the solvent sets NP size by controlling the extent of dynamic growth up to growth arrest. An a priori model based on spinodal decomposition corroborates our proposed mechanism, explaining how size scales with the solvent-dependent critical water fraction of growth arrest and enabling more efficient NP engineering.

Unimer Exchange Is not Necessary for Morphological Transitions in Polymerization‐Induced Self‐Assembly

“…Interestingly, it has been proposed in the literature that the presence of solvent, monomer or molecules with similar chemical structure may help morphological transitions. [44][45][46][47][48][49][50] On the one hand, we have demonstrated that the presence of toluene in a typical emulsion polymerization of styrene via PISA has a great impact on the morphologies formed; [50] on the other hand, the addition of plasticizing solvents postpolymerization (to particles obtained by PISA or mini-or nanoemulsion) was extensively explored by the groups of Davis [44] and Anastasaki. [45] For instance, the latter showed that the addition of toluene in an aqueous dispersion of nano-objects comprising a polystyrene solvophobic block can trigger quick transitions toward higher order morphologies.…”

In situ monitoring of block copolymer self-assembly through con-trolled dialysis with light and neutron scattering detection

“…The dynamics of the polymer chains is also maximal at the beginning of the dialysis when the THF fraction is high. 18,20,45 Both these conditions probably favor the early BC self-assembly into vesicles following a different pathway among the multiple metastable states that can exist in the free energy landscape of a BC system. 19,46,47 Modifying the membrane porosity is therefore a simple way to perform self-assembly under kinetic or thermodynamic control which can be of interest for many polymer and colloidal systems.…”

“…16,17 A recurring issue with the solvent exchange method is the equilibrium state of BC aggregates, which depends not only on the final water content but also on the magnitude and rate of the water jump. 14,[18][19][20] In order to promote the formation of equilibrium morphologies, as expected for phase diagrams, water should be added slowly and gradually, by analogy with the conditions used for annealing in bulk studies. 21 A fast and large water jump can lead to kinetically arrested morphologies, which is the basis to form BC nanoparticles by the so-called flash nanoprecipitation technique.…”

Unimer Exchange Is not Necessary for Morphological Transitions in Polymerization‐Induced Self‐Assembly

“…Interestingly, it has been proposed in the literature that the presence of solvent, monomer or molecules with similar chemical structure may help morphological transitions. [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ] On the one hand, we have demonstrated that the presence of toluene in a typical emulsion polymerization of styrene via PISA has a great impact on the morphologies formed; [50] on the other hand, the addition of plasticizing solvents post‐polymerization (to particles obtained by PISA or mini‐ or nanoemulsion) was extensively explored by the groups of Davis [44] and Anastasaki. [45] For instance, the latter showed that the addition of toluene in an aqueous dispersion of nano‐objects comprising a polystyrene solvophobic block can trigger quick transitions toward higher order morphologies.…”