The encapsulation of liquid crystalline phases, formed from biocompatible amphiphiles, into nanoparticles has emerged as a promising delivery strategy for hydrophilic and hydrophobic therapeutics. Strategies to characterize these delivery systems as a function of formulation parameters and aqueous environment post-manufacture are well-documented. A critical gap remains regarding the assembly kinetics and in situ dynamics of these systems using industrially relevant manufacturing techniques. Systematically investigating these characteristics is challenging: computational simulations are time-intensive and costly, while current in situ quantification techniques are limited in scalability and batch size. We here combine synchrotron small-angle X-ray scattering with Flash NanoPrecipitation, a scalable turbulent mixing technology, to capture time-resolved measurements of the formation of liquid crystal phases under nanoconfinement during and after nanoprecipitation. This technique reveals that self-assembly occurs in two steps, with internal liquid crystal self-assembly occurring on longer time scales (seconds to minutes) than initial nanoprecipitation (milliseconds) as a function of formulation parameters.
Keywords: Flash NanoPrecipitation; Nanoparticles; X-ray scattering; drug delivery; liquid crystal assembly kinetics.