title: High-Throughput Screening of Saturated Fatty Acid Influence on Nanostructure of Lyotropic Liquid Crystalline Lipid Nanoparticles.
abstract: Self-assembled lyotropic liquid crystalline lipid nanoparticles have been developed for a wide range of biomedical applications with an emerging focus for use as delivery vehicles for drugs, genes, and in vivo imaging agents. In this study, we report the generation of lipid nanoparticle libraries with information regarding mesophase and lattice parameter, which can aid the selection of formulation for a particular end-use application. In this study we elucidate the phase composition parameters that influence the internal structure of lipid nanoparticles produced from monoolein, monopalmitolein and phytantriol incorporating a variety of saturated fatty acids (FA) with different chain lengths at varying concentrations and temperatures. The material libraries were established using high throughput formulation and screening techniques, including synchrotron small-angle X-ray scattering. The results demonstrate the rich polymorphism of lipid nanoparticles with nonlamellar mesophases in the presence of saturated FAs. The inclusion of saturated FAs within the lipid nanoparticles promotes a gradual phase transition at all temperatures studied toward structures with higher negative surface curvatures (e.g., from inverse bicontinuous cubic phase to hexagonal phase and then emulsified microemulsion). The three partial phase diagrams produced are discussed in terms of the influence of FA chain length and concentration on nanoparticle internal mesophase structure and lattice parameters. The study also highlights a compositionally dependent coexistence of multiple mesophases, which may indicate the presence of multicompartment nanoparticles containing cubic/cubic and cubic/hexagonal mesophases.
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.|SAXS/WAXS Beamline, Australian Synchrotron , Clayton, Victoria 3168 Australia.
authors.forename: Nhiem
authors.initials: N
authors.lastname: Tran
authors.affiliation: SAXS/WAXS Beamline, Australian Synchrotron , Clayton, Victoria 3168 Australia.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Hawley
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhai
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Muir
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.
authors.forename: Celesta
authors.initials: C
authors.lastname: Fong
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.|School of Applied Sciences, College of Science, Engineering and Health, RMIT University , Melbourne, Victoria 3000 Australia.
authors.forename: Calum J
authors.initials: CJ
authors.lastname: Drummond
authors.affiliation: CSIRO Manufacturing , Clayton, Victoria 3168 Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet