Deuterated phytantriol - A versatile compound for probing material distribution in liquid crystalline lipid phases using neutron scattering

Nageshwar R Yepuri; Andrew J Clulow; Richard N Prentice; Elliot P Gilbert; Adrian Hawley; Shakila B Rizwan; Ben J Boyd; Tamim A Darwish

doi:10.1016/j.jcis.2018.09.022

Deuterated phytantriol - A versatile compound for probing material distribution in liquid crystalline lipid phases using neutron scattering

J Colloid Interface Sci. 2019 Jan 15:534:399-407. doi: 10.1016/j.jcis.2018.09.022. Epub 2018 Sep 7.

Authors

Nageshwar R Yepuri¹, Andrew J Clulow², Richard N Prentice³, Elliot P Gilbert⁴, Adrian Hawley⁵, Shakila B Rizwan³, Ben J Boyd⁶, Tamim A Darwish⁷

Affiliations

¹ National Deuteration Facility, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
² Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Victoria 3052, Australia.
³ School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
⁴ Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
⁵ Australian Synchrotron, ANSTO, 800 Blackburn Road, Clayton, Victoria 3168, Australia.
⁶ Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Victoria 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: ben.boyd@monash.edu.
⁷ National Deuteration Facility, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia. Electronic address: tamim.darwish@ansto.gov.au.

PMID: 30245337
DOI: 10.1016/j.jcis.2018.09.022

Abstract

Phytantriol is an interfacially-active lipid that is chemically robust, non-digestible and forms particles with internal bicontinuous cubic phase structures (cubosomes) when dispersed with non-ionic surfactants at ambient and physiological temperatures. The liquid crystalline internal structure of phytantriol-based cubosomes can be changed to alter the interfacial contact area/topology with the aqueous dispersant to trigger bioactive payload release or to alter the local membrane curvature around bound or embedded proteins. To enable the study of payload distribution, structure and transformation kinetics within phytantriol particles by neutron scattering techniques it is desirable to have access to a deuterated version of this molecule but to date a synthetic route has not been available. The first successful synthesis of phytantriol-d₃₉ is presented here alongside a preliminary physical characterisation of related particle structures when phytantriol-d₃₉ is dispersed using two non-ionic surfactants, Tween® 80 and Pluronic® F127. Synchrotron small angle X-ray scattering (SAXS) was used to confirm that phytantriol-d₃₉-based nanoparticles in D₂O form similar liquid crystalline structures to those of their natural isotopic abundance (phytantriol/H₂O) counterparts as a function of temperature. Finally, small angle neutron scattering (SANS) with solvent contrast to match out the phytantriol-d₃₉ structuring was used to show that the spatial correlations between the Tween® and Pluronic® non-ionic surfactant molecules are different within dispersed phytantriol-d₃₉ particles with different liquid crystalline structures in D₂O. The surfactant molecules in phytantriol-d₃₉/Tween® 80 particles with Im3m cubic structures were found to follow a self-avoiding walk, whereas in phytantriol-d₃₉/Pluronic® F127 particles with Pn3m cubic structures they were found to follow a more rod-like packing arrangement.

Keywords: Contrast matching; Cubosome; Deuterated; Phytantriol; Small angle neutron scattering.