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Interactions of Choline and Geranate (CAGE) and Choline Octanoate (CAOT) Deep Eutectic Solvents with Lipid Bilayers

Neville, George M. LU ; Dobre, Ana Maria ; Smith, Gavin J. ; Micciulla, Samantha ; Brooks, Nick J. ; Arnold, Thomas ; Welton, Tom and Edler, Karen J. LU orcid (2023) In Advanced Functional Materials
Abstract

Mixtures between choline and geranic acid (CAGE) have previously been shown to insert into lipid bilayers. This may be useful for the transdermal delivery of larger pharmaceuticals, however, little is known about the mechanism of activity. By comparing the interactions between CAGE and lipid bilayers with those of a less-active, yet closely-related analogue, choline octanoic acid (CAOT), a chemical basis can be investigated. Overall, six systems are studied here by neutron reflectivity, where d54-1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) solid-supported phospholipid bilayers are first formed on SiO2 substrates before exposure to the deep eutectic solvent (DES). Components of the DES could be identified... (More)

Mixtures between choline and geranic acid (CAGE) have previously been shown to insert into lipid bilayers. This may be useful for the transdermal delivery of larger pharmaceuticals, however, little is known about the mechanism of activity. By comparing the interactions between CAGE and lipid bilayers with those of a less-active, yet closely-related analogue, choline octanoic acid (CAOT), a chemical basis can be investigated. Overall, six systems are studied here by neutron reflectivity, where d54-1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) solid-supported phospholipid bilayers are first formed on SiO2 substrates before exposure to the deep eutectic solvent (DES). Components of the DES could be identified within the bilayer by exploiting contrast variation and selective deuteration. CAGE is shown to be a mild disruptive agent, free to insert and diffuse across the bilayer, preserving much of the bilayer integrity. Experiments identify co-mingling of geranate ions inhibits the efficient packing of lipid tails, increasing hydration across the bilayer. Conversely, CAOT is found to both exchange and remove lipid molecules to achieve incorporation, inducing swelling and the formation of solvent patches. It appears these behaviors derive from the structures of the anions and thus amphiphilicity of the DES, laying the foundations for the rational design and optimization of these candidates toward transdermal delivery.

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organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
deep eutectic solvents, ionic liquids, lipid bilayers, neutron reflectivity, transdermal delivery
in
Advanced Functional Materials
publisher
Wiley-Blackwell
external identifiers
  • scopus:85172862273
ISSN
1616-301X
DOI
10.1002/adfm.202306644
language
English
LU publication?
yes
id
b654beff-7c83-45da-8f96-484c6649e575
date added to LUP
2023-10-20 14:14:53
date last changed
2023-10-23 14:57:21
@article{b654beff-7c83-45da-8f96-484c6649e575,
  abstract     = {{<p>Mixtures between choline and geranic acid (CAGE) have previously been shown to insert into lipid bilayers. This may be useful for the transdermal delivery of larger pharmaceuticals, however, little is known about the mechanism of activity. By comparing the interactions between CAGE and lipid bilayers with those of a less-active, yet closely-related analogue, choline octanoic acid (CAOT), a chemical basis can be investigated. Overall, six systems are studied here by neutron reflectivity, where d<sub>54</sub>-1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) solid-supported phospholipid bilayers are first formed on SiO<sub>2</sub> substrates before exposure to the deep eutectic solvent (DES). Components of the DES could be identified within the bilayer by exploiting contrast variation and selective deuteration. CAGE is shown to be a mild disruptive agent, free to insert and diffuse across the bilayer, preserving much of the bilayer integrity. Experiments identify co-mingling of geranate ions inhibits the efficient packing of lipid tails, increasing hydration across the bilayer. Conversely, CAOT is found to both exchange and remove lipid molecules to achieve incorporation, inducing swelling and the formation of solvent patches. It appears these behaviors derive from the structures of the anions and thus amphiphilicity of the DES, laying the foundations for the rational design and optimization of these candidates toward transdermal delivery.</p>}},
  author       = {{Neville, George M. and Dobre, Ana Maria and Smith, Gavin J. and Micciulla, Samantha and Brooks, Nick J. and Arnold, Thomas and Welton, Tom and Edler, Karen J.}},
  issn         = {{1616-301X}},
  keywords     = {{deep eutectic solvents; ionic liquids; lipid bilayers; neutron reflectivity; transdermal delivery}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Advanced Functional Materials}},
  title        = {{Interactions of Choline and Geranate (CAGE) and Choline Octanoate (CAOT) Deep Eutectic Solvents with Lipid Bilayers}},
  url          = {{http://dx.doi.org/10.1002/adfm.202306644}},
  doi          = {{10.1002/adfm.202306644}},
  year         = {{2023}},
}