The effect of lipid composition on the thermal stability of nanodiscs.

Discoidal lipid nanoparticles (LNPs) called Nanodiscs (NDs) are derived from human high-density lipoprotein (HDL). Such biomimetics are ideally suited for the stabilization and delivery of pharmaceuticals, including chemicals, bio-active proteins and vaccines. The stability and circulation lifetimes of reconstituted HDL nanoparticles, including NDs, are variable. Lipids found in thermophilic archaea and bacteria are prime candidates for the stabilization of LNPs. We report the thermal stability of NDs prepared with lipids that differ in saturation, have either ether- or ester linkages between the fatty acid and glycerol backbone or contain isoprenoid fatty acid tails (phytanyl lipids). NDs with two saturated fatty acids show a much greater long-term thermostability than NDs with an unsaturated fatty acid. Ether fatty acid linkages, commonly found in thermophiles, did not improve stability of NDs compared to ester fatty acid linkages when using saturated lipids. NDs containing phytanyl and saturated alkyl fatty acids show similar stability at 37 °C. NDs assembled with phytanyl lipids contain three copies of the membrane scaffolding protein as opposed to the canonical dimer found in conventional NDs. The findings present a strong basis for the production of thermostable NDs through the selection of appropriate lipids and are likely broadly applicable to LNP development.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcellus Ubbink reports financial support was provided by The Dutch Research Council (NWO). Marcellus Ubbink reports a relationship with Batavia Biosciences BV that includes: funding grants. Marcellus Ubbink reports a relationship with ZoBio BV that includes: funding grants. The authors disclose a potential competing interest due to an ongoing patent filing related to the topics discussed in this study. The project was funded by the Dutch Research Council with financial contributions by Batavia Biosciences B.V. and ZoBio B.V.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)