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Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics

BACKGROUND: Solvate ionic liquids (SILs) are a new class of ionic liquids that are equimolar solutions of lithium bistrifluoromethanesulfonimide in either triglyme or tetraglyme, referred to as G3LiTFSA and G4LiTFSA, respectively. SILs play a role in energy storage lithium batteries, and have been p...

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Autores principales: Yoganantharajah, Prusothman, Ray, Alexander P., Eyckens, Daniel J., Henderson, Luke C., Gibert, Yann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975478/
https://www.ncbi.nlm.nih.gov/pubmed/29843701
http://dx.doi.org/10.1186/s12896-018-0442-1
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author Yoganantharajah, Prusothman
Ray, Alexander P.
Eyckens, Daniel J.
Henderson, Luke C.
Gibert, Yann
author_facet Yoganantharajah, Prusothman
Ray, Alexander P.
Eyckens, Daniel J.
Henderson, Luke C.
Gibert, Yann
author_sort Yoganantharajah, Prusothman
collection PubMed
description BACKGROUND: Solvate ionic liquids (SILs) are a new class of ionic liquids that are equimolar solutions of lithium bistrifluoromethanesulfonimide in either triglyme or tetraglyme, referred to as G3LiTFSA and G4LiTFSA, respectively. SILs play a role in energy storage lithium batteries, and have been proposed as potential alternatives to traditional organic solvents such as DMSO. G3TFSA and G4TFSA have been shown to exhibit no toxicity in vivo up to 0.5% (v/v), and solubilize small compounds (N,N-diethylaminobenzaldehyde) with full penetrance, similar to DMSO delivered DEAB. Herein, we compare the effects of storage (either at room temperature or − 20 °C) on DEAB solubilized in either DMSO, G3TFSA or G4TFSA to investigate compound degradation and efficacy. RESULTS: The findings show that DEAB stored at room temperature (RT) for 4 months solubilized in either G3TFSA, G4TFSA or DMSO displayed no loss of penetrance. The same was observed with stock solutions stored at − 20 °C for 4 months; however G4TFSA remained in a liquid state compared to both G3TFSA and DMSO. Moreover, we examined the ability of G3TFSA and G4TFSA to solubilize another small molecular therapeutic, the FGFR antagonist SU5402. G4TFSA, unlike G3TFSA solubilized SU5402 and displayed similar phenotypic characteristics and reduced dlx2a expression as reported and shown with SU5402 in DMSO; albeit more penetrative. CONCLUSION: This study validates the use of these ionic liquids as a potential replacement for DMSO in vivo as organic solubilizing agents.
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spelling pubmed-59754782018-05-31 Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics Yoganantharajah, Prusothman Ray, Alexander P. Eyckens, Daniel J. Henderson, Luke C. Gibert, Yann BMC Biotechnol Research Article BACKGROUND: Solvate ionic liquids (SILs) are a new class of ionic liquids that are equimolar solutions of lithium bistrifluoromethanesulfonimide in either triglyme or tetraglyme, referred to as G3LiTFSA and G4LiTFSA, respectively. SILs play a role in energy storage lithium batteries, and have been proposed as potential alternatives to traditional organic solvents such as DMSO. G3TFSA and G4TFSA have been shown to exhibit no toxicity in vivo up to 0.5% (v/v), and solubilize small compounds (N,N-diethylaminobenzaldehyde) with full penetrance, similar to DMSO delivered DEAB. Herein, we compare the effects of storage (either at room temperature or − 20 °C) on DEAB solubilized in either DMSO, G3TFSA or G4TFSA to investigate compound degradation and efficacy. RESULTS: The findings show that DEAB stored at room temperature (RT) for 4 months solubilized in either G3TFSA, G4TFSA or DMSO displayed no loss of penetrance. The same was observed with stock solutions stored at − 20 °C for 4 months; however G4TFSA remained in a liquid state compared to both G3TFSA and DMSO. Moreover, we examined the ability of G3TFSA and G4TFSA to solubilize another small molecular therapeutic, the FGFR antagonist SU5402. G4TFSA, unlike G3TFSA solubilized SU5402 and displayed similar phenotypic characteristics and reduced dlx2a expression as reported and shown with SU5402 in DMSO; albeit more penetrative. CONCLUSION: This study validates the use of these ionic liquids as a potential replacement for DMSO in vivo as organic solubilizing agents. BioMed Central 2018-05-29 /pmc/articles/PMC5975478/ /pubmed/29843701 http://dx.doi.org/10.1186/s12896-018-0442-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yoganantharajah, Prusothman
Ray, Alexander P.
Eyckens, Daniel J.
Henderson, Luke C.
Gibert, Yann
Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title_full Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title_fullStr Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title_full_unstemmed Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title_short Comparison of solvate ionic liquids and DMSO as an in vivo delivery and storage media for small molecular therapeutics
title_sort comparison of solvate ionic liquids and dmso as an in vivo delivery and storage media for small molecular therapeutics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975478/
https://www.ncbi.nlm.nih.gov/pubmed/29843701
http://dx.doi.org/10.1186/s12896-018-0442-1
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