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Two refined clay minerals, English China Clay (predominantly kaolinite) and Wyoming Bentonite (predominantly sodium-montmorillonite), were used to assess the time-dependent effects of mineral structural chemistry on the lime–clay reaction. The two clays, representing the extremes of structural negative charge development, were treated with two lime contents. Changes in the physico-chemistry of the samples were monitored after three curing periods by performing batch leaching tests and monitoring changes in undrained shear strength and Atterberg limits. The effects of changing the batch test operating parameters and increasing the curing period were assessed by measuring changes in solution pH and conductivity, and by analysis of eight elements in solution. The solidification mechanisms due to lime addition were found to be different for the two minerals. Pozzolanic reactions involving English China Clay and Wyoming Bentonite were found to occur owing to the dissolution of aluminium and silicon from the respective mineral. Development of the batch leaching test showed that changing the operational parameters had no effect on the observed trends associated with the time-dependent modification and solidification reactions. It was also shown that successful solidification could be monitored using simple conductivity measurements without the need for extensive and complex elemental analysis.

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Lipid nanoparticles (LNPs) are a leading platform for therapeutic delivery of small interfering RNAs (siRNAs). Optimization of LNPs as therapeutic products is enabled by the development of structure-activity relationships (SAR) linking LNP physiochemical and macromolecular properties to bioperformance. Methods by which LNP properties can be rationally manipulated are thus critical enablers of this fundamental knowledge build. In this work, we present a mechanistic study of LNP self-assembly via a rapid antisolvent precipitation process and identify critical physiochemical and kinetic parameters governing the evolution of LNP three-dimensional macromolecular structure as a biorelevant SAR feature. Using small-angle X-ray scattering, LNPs are shown to undergo a temporal evolution in macromolecular structure during self-assembly, rearranging from initially disordered phases after precipitation into well-ordered structures following a necessary annealing stage of the assembly sequence. The ability of LNPs to undergo structural reorganization is shown to be effected by the chemical nature of the aqueous antisolvent used for precipitation. Antisolvents of varying buffering species differentially influence LNP macromolecular features, revealing a new participatory role of buffer ions in LNP self-assembly. Furthermore, the formation of macromolecular structure in LNPs is shown to improve the efficiency of siRNA encapsulation, thereby offering a simple, nonchemical route for preparation of high-payload LNPs that minimize the dose of lipid excipients. The developed LNP precipitation process and mechanistic understanding of self-assembly are shown to be generalizable, enabling the production of LNPs with a tunable range of macromolecular features, as evidenced by the cubic, hexagonal, and oligo-lamellar phase LNPs exemplarily generated.

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