  The self-assembly of copolymeric vesicles and micelles in micromixers is
studied by External Potential Dynamics (EPD) simulations -- a dynamic density
functional approach that explicitly accounts for the polymer architecture both
at the level of thermodynamics and dynamics. Specifically, we focus on the
co-solvent method, where nanoparticle precipitation is triggered by mixing a
poor co-solvent into a homogeneous copolymer solution in a micromixer.
Experimentally, it has been reported that the flow rate in the micromixers
influences the size of the resulting particles as well as their morphology: At
small flow rates, vesicles dominate; with increasing flow rate, more and more
micelles form, and the size of the particles decreases. Our simulation model is
based on the assumption that the flow rate mainly sets the rate of mixing of
solvent and co-solvent. The simulations reproduce the experimental observations
at an almost quantitative level and provide insight into the underlying
physical mechanisms: First, they confirm an earlier conjecture according to
which the size control takes place in the earliest stage of the particle
self-assembly, during the spinodal decomposition of polymers and solvent.
Second, they reveal a crossover between different morphological regimes as a
function of mixing rate. Hence they demonstrate that varying the mixing rate in
a co-solvent setup is an effective way to control two key properties of drug
delivery systems, their mean size and their morphology.
