Nageshwar R. Yepuri, Andrew J. Clulow, Richard N. Prentice, Elliot P. Gilbert, Adrian Hawley, Shakila B. Rizwan, Ben J. Boyd, Tamim Darwish
Journal of Colloid and Interface Science 2019, 534, 399-407 DOI: 10.1016/j.jcis.2018.09.022
Amphiphilic lipids have the potential to form inverse hexagonal and cubic liquid crystalline phases when they are hydrated by the penetration of organised water channels into the lipid matrix. They have garnered much interest due to their potential to act as biocompatible, environment-responsive delivery vehicles for hydrophobic drugs and membrane-bound peptides/proteins.
Phytantriol is a versatile lipid that forms cubic and hexagonal phases under treatment-relevant conditions and this can be used as a switch to trigger controlled drug release. Phytantriol is also an interfacially-active lipid used by the cosmetics industry that is chemically robust, non-digestible and tends to form particles with bicontinuous cubic phase structures when dispersed with non-ionic surfactants.
To develop effective dosing strategies, phytantriol particles are dispersed in aqueous solution using surfactants to stabilise the large interfacial area formed by internal water channels within the structured lipid particles.
In a recent publication in the Journal of Colloid and Interface Science, researchers from the Monash Institute of Pharmaceutical Sciences, University of Otago and ANSTO, studied deuterated phytantriol-d39 using small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) to confirm that the dispersed nanoparticles comprising phytantriol-d39 in D2O formed similar liquid crystalline phases as their natural isotopic abundance counterparts.
SANS is an ideal technique for probing the structuring of non-ionic surfactants that stabilise phytantriol-based liquid crystalline particles.
In addition, using deuterated phytantriol, it is possible to obtain excellent contrast between different materials and organic liquid crystalline particles, which enables better resolution of the interfaces within the samples and of the changes that occur.
In this investigation, researchers from the National Deuteration Facility demonstrated the first viable synthesis for the preparation of phytantriol-d39 from phytanic acid. The deuterated version of phytantriol reproduced the liquid crystalline phases observed for hydrogenous phytantriol when dispersed in D2O with Pluronic F127 and Tween 80.
For the first time, the structuring of non-ionic surfactants that stabilise phytantriol-based liquid crystalline particles has been observed by SANS. The different cubic phase structures formed by these two surfactants at room temperature correspond to different organisation of the surfactant stabilisers within cubosomes comprising different intertwining channel structures.
The highly-deuterated phytantriol-d39 described can be used to distinguish or remove signals from phytantriol in nuclear magnetic resonance spectroscopic, mass spectrometric and neutron scattering investigations.
These studies show the strong potential for phytantriol-d39 to play a leading role in the future understanding of the molecular-level interactions of nanostructured particles with blood plasma proteins, exogenous surfactants used as excipients/co-dispersants, components of the digestive milieu and drugs.