Time-Resolved In Situ Small-Angle X-ray Scattering to Determine the Kinetics of Formation of Liquid Crystalline Structure in the Core of Polymeric Nanoparticles during and after Turbulent Mixing

• DOI: 10.1021/acs.nanolett.5c01095
• Publication Date: 2025-04-16T16:21:06Z
• Authors: Sophia R. Dasaro; Lucas D. Johnson; Malinda Salim; Vincent He; David Amelemah; Ellie Ponsonby-Th...; Bryce Barber; Wye-Khay Fong; Jonathan Caukwell; Elizabeth Peach; Ben Li; Livia Salvati Manni; Nigel Kirby; Gregory G. Warr; Robert K. Prud’homme; Ben J. Boyd; Kurt Ristroph
• Keywords: Small-angle X-ray scattering

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 systems function formulation parameters aqueous environment post-manufacture are well-documented. A critical gap remains regarding the assembly kinetics in situ dynamics using industrially relevant manufacturing techniques. Systematically investigating characteristics is challenging: computational simulations time-intensive costly, while current quantification techniques limited scalability batch size. We here combine synchrotron small-angle X-ray scattering with Flash NanoPrecipitation, scalable turbulent mixing technology, capture time-resolved measurements formation crystal phases under nanoconfinement during after nanoprecipitation. This technique reveals that self-assembly occurs two steps, internal occurring on longer time scales (seconds minutes) than initial nanoprecipitation (milliseconds) parameters.