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

George M. Neville; Ana-Maria Dobre; Gavin J. Smith; Samantha Micciulla; Nick J. Brooks; Thomas Arnold; Tom Welton; Karen J. Edler

doi:10.1002/adfm.202306644

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

George M. Neville, Ana-Maria Dobre, Gavin J. Smith, Samantha Micciulla, Nick J. Brooks, Thomas Arnold, Tom Welton, Karen J. Edler

Research output: Contribution to journal › Article › peer-review

1 Citation (SciVal)

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 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.

Original language	English
Article number	2306644
Journal	Advanced Functional Materials
Volume	34
Issue number	2
Early online date	2 Oct 2023
DOIs	https://doi.org/10.1002/adfm.202306644
Publication status	Published - 9 Jan 2024

Bibliographical note

Funding Information:
This work was supported by the Engineering and Physical Sciences Research Council EP/L016354/1. The authors thank GlaxoSmithKline Biologics S.A. for supporting studentship funding for Ana‐Maria Dobre. G.S. acknowledges support from the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (NIHR‐INF‐1654). The ILL is acknowledged for the award of beamtime on FIGARO (Raw experiment data is available at: https://doi.ill.fr/10.5291/ILL‐DATA.9‐13‐927 ) and granting access to the Partnership for Soft Condensed Matter (PSCM) laboratories, where sample preparation was performed. The authors would like to thank Dr. Mario Campana, Dr. Luke Clifton, and Dr. Stephen Hall (ISIS Neutron and Muon Source, UK) for their invaluable guidance in forming solid‐supported lipid bilayers, Dr. Andrew McCluskey (European Spallation Source) for assistance in the use of Bayesian inference to interpret reflectivity data and Prof. Pedro Estrela (University of Bath) for providing the QCM‐D sensor module. Data supporting this manuscript can be downloaded from the University of Bath Research repository: https://doi.org/10.15125/BATH‐01289 .

Funding

This work was supported by the Engineering and Physical Sciences Research Council EP/L016354/1. The authors thank GlaxoSmithKline Biologics S.A. for supporting studentship funding for Ana‐Maria Dobre. G.S. acknowledges support from the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (NIHR‐INF‐1654). The ILL is acknowledged for the award of beamtime on FIGARO (Raw experiment data is available at: https://doi.ill.fr/10.5291/ILL‐DATA.9‐13‐927 ) and granting access to the Partnership for Soft Condensed Matter (PSCM) laboratories, where sample preparation was performed. The authors would like to thank Dr. Mario Campana, Dr. Luke Clifton, and Dr. Stephen Hall (ISIS Neutron and Muon Source, UK) for their invaluable guidance in forming solid‐supported lipid bilayers, Dr. Andrew McCluskey (European Spallation Source) for assistance in the use of Bayesian inference to interpret reflectivity data and Prof. Pedro Estrela (University of Bath) for providing the QCM‐D sensor module. Data supporting this manuscript can be downloaded from the University of Bath Research repository: https://doi.org/10.15125/BATH‐01289 . This work was supported by the Engineering and Physical Sciences Research Council EP/L016354/1. The authors thank GlaxoSmithKline Biologics S.A. for supporting studentship funding for Ana-Maria Dobre. G.S. acknowledges support from the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (NIHR-INF-1654). The ILL is acknowledged for the award of beamtime on FIGARO (Raw experiment data is available at: https://doi.ill.fr/10.5291/ILL-DATA.9-13-927) and granting access to the Partnership for Soft Condensed Matter (PSCM) laboratories, where sample preparation was performed. The authors would like to thank Dr. Mario Campana, Dr. Luke Clifton, and Dr. Stephen Hall (ISIS Neutron and Muon Source, UK) for their invaluable guidance in forming solid-supported lipid bilayers, Dr. Andrew McCluskey (European Spallation Source) for assistance in the use of Bayesian inference to interpret reflectivity data and Prof. Pedro Estrela (University of Bath) for providing the QCM-D sensor module. Data supporting this manuscript can be downloaded from the University of Bath Research repository: https://doi.org/10.15125/BATH-01289.

Funders	Funder number
NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards
University of Bath Research
Engineering and Physical Sciences Research Council	NIHR‐INF‐1654, EP/L016354/1
ISIS Neutron and Muon Source

Keywords

deep eutectic solvents
ionic liquids
lipid bilayers
neutron reflectivity
transdermal delivery

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Condensed Matter Physics
General Chemistry
General Materials Science
Electrochemistry
Biomaterials

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10.1002/adfm.202306644Licence: CC BY

Cite this

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

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 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.",

keywords = "deep eutectic solvents, ionic liquids, lipid bilayers, neutron reflectivity, transdermal delivery",

author = "Neville, {George M.} and Ana-Maria Dobre and Smith, {Gavin J.} and Samantha Micciulla and Brooks, {Nick J.} and Thomas Arnold and Tom Welton and Edler, {Karen J.}",

note = "Funding Information: This work was supported by the Engineering and Physical Sciences Research Council EP/L016354/1. The authors thank GlaxoSmithKline Biologics S.A. for supporting studentship funding for Ana‐Maria Dobre. G.S. acknowledges support from the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (NIHR‐INF‐1654). The ILL is acknowledged for the award of beamtime on FIGARO (Raw experiment data is available at: https://doi.ill.fr/10.5291/ILL‐DATA.9‐13‐927 ) and granting access to the Partnership for Soft Condensed Matter (PSCM) laboratories, where sample preparation was performed. The authors would like to thank Dr. Mario Campana, Dr. Luke Clifton, and Dr. Stephen Hall (ISIS Neutron and Muon Source, UK) for their invaluable guidance in forming solid‐supported lipid bilayers, Dr. Andrew McCluskey (European Spallation Source) for assistance in the use of Bayesian inference to interpret reflectivity data and Prof. Pedro Estrela (University of Bath) for providing the QCM‐D sensor module. Data supporting this manuscript can be downloaded from the University of Bath Research repository: https://doi.org/10.15125/BATH‐01289 . ",

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AU - Neville, George M.

AU - Dobre, Ana-Maria

AU - Smith, Gavin J.

AU - Micciulla, Samantha

AU - Brooks, Nick J.

AU - Arnold, Thomas

AU - Welton, Tom

AU - Edler, Karen J.

N1 - Funding Information: This work was supported by the Engineering and Physical Sciences Research Council EP/L016354/1. The authors thank GlaxoSmithKline Biologics S.A. for supporting studentship funding for Ana‐Maria Dobre. G.S. acknowledges support from the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (NIHR‐INF‐1654). The ILL is acknowledged for the award of beamtime on FIGARO (Raw experiment data is available at: https://doi.ill.fr/10.5291/ILL‐DATA.9‐13‐927 ) and granting access to the Partnership for Soft Condensed Matter (PSCM) laboratories, where sample preparation was performed. The authors would like to thank Dr. Mario Campana, Dr. Luke Clifton, and Dr. Stephen Hall (ISIS Neutron and Muon Source, UK) for their invaluable guidance in forming solid‐supported lipid bilayers, Dr. Andrew McCluskey (European Spallation Source) for assistance in the use of Bayesian inference to interpret reflectivity data and Prof. Pedro Estrela (University of Bath) for providing the QCM‐D sensor module. Data supporting this manuscript can be downloaded from the University of Bath Research repository: https://doi.org/10.15125/BATH‐01289 .

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

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

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

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

Cite this