Millisecond Phase Transition Kinetics of Lyotropic Liquid Crystalline Nanoparticles Observed by Time-Resolved Small Angle X-ray Solution Scattering

Abstract

This study investigates the dynamic behavior of lyotropic liquid crystal nanoparticles (LCNPs), which are widely recognized for their applications in drug delivery. By employing nanosecond near-infrared laser pulse-induced temperature jump (T-jump) and time-resolved X-ray solution scattering, the structural dynamics of phase transitions in phytantriol-based cubosomes and hexosomes are revealed. Both cubosome and hexosome LCNPs undergo phase transitions into noncrystalline phases at high temperatures. Their phase transition kinetics, occurring within milliseconds (ms) and involving one intermediate structure, are captured. Additionally, the reverse self-assembly processes of LCNPs were observed, occurring on the timescale of a few hundred ms. To our knowledge, this is the first observation of LCNP T-jump induced phase transitions on the ms timescale and their reverse self-assembly. These findings provide valuable insights into the LCNP phase transition processes, with potential implications for drug delivery applications.

Keywords: lyotropic liquid crystal nanoparticle; phase transition kinetics; temperature jump; time‐resolved X‐ray solution scattering.

Figure 1

The DLS size distribution, with amplitudes plotted as the normalized fractional population, is shown for cubosomes (C) and hexosomes (H).

Figure 2

a,b) Static SAXS temperature series for the a) cubosome LCNPs and b) hexosome LCNPs are shown. The numbered peaks correspond to Bragg diffraction peaks, representing the internal structures of the LCNPs, specifically the cubosomes and hexosomes.

Figure 3

The SAXS data differences after the T‐jump, with representative time delays: a) cubosomes and b) hexosomes. The initial temperatures were 55 °C for cubosomes and 40 °C for hexosomes, with an estimated T‐jump magnitude of ≈7.5 °C. The data reveal the disappearance of crystalline peaks, the growth of the noncrystalline phase signal, and subsequent decay, ultimately returning to their original phases. The red line represents the fitting signal discussed below.

Figure 4

The results of kinetic fitting for cubosomes are shown in a) and c), while those for hexosomes are presented in b) and d). The corresponding species associated with these fits are depicted in (a) and (b), and the kinetic traces are visualized in (c) and (d). Notably, the initial species (I _C and I _H) undergo rapid growth immediately following the T‐jump, followed by a subsequent decay coincides with the emergence of the product state. The product state represents the noncrystalline structure formed after the phase transition, which then decays on a time scale of ≈100 ms. The intermediate state corresponds to the phase‐shifted structure that arises just before the phase transition occurs.