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Updated: Jun 21, 2026

Development, Characterization, and Evaluation of CAGE-based Ionic Liquid Systems for Transdermal Delivery
Published on: September 26, 2025
Biocompatible ionic liquids: a new approach for stabilizing proteins in liquid formulation.
Regina M Vrikkis1, Kevin J Fraser, Kyoko Fujita
1Department of Mechanical Engineering, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA. rmkemp@uncc.edu
Ionic liquids (ILs) show promise for stabilizing therapeutic proteins. Biocompatible ILs, like choline dihydrogen phosphate (choline dhp), demonstrated low cytotoxicity and enhanced protein stability, suggesting potential for drug formulation.
Area of Science:
- Biochemistry
- Materials Science
- Pharmacology
Background:
- Ionic liquids (ILs) offer potential for stabilizing proteins in therapeutic formulations.
- Assessing the biocompatibility of ILs is crucial for clinical translation.
- Protein-based drugs are a growing area in modern medicine.
Purpose of the Study:
- To investigate the cytotoxicity of rationally synthesized ILs.
- To evaluate the protein-stabilizing capabilities of specific ILs.
- To explore the potential of biocompatible ILs in liquid drug formulations.
Main Methods:
- Cytotoxicity assessed using resazurin reduction assay on J774 macrophage cell line.
- Protein structural stability evaluated using differential scanning microcalorimetry (DSC).
- Functional activity of lysozyme assessed via Micrococcus lysodiekticus activity test.
Main Results:
- Toxicity order found to be choline dihydrogen phosphate (choline dhp) < choline saccharinate < 1-butyl 3-methyl imidazolium lactate (bmim lactate).
- Lysozyme stored in 80 wt% choline dhp (aq) showed higher activity and folded fraction after 1 month compared to aqueous buffer controls.
- All tested ILs exhibited relatively benign biocompatibility profiles.
Conclusions:
- Biocompatibility and protein stabilization can be rationally designed into ILs.
- Choline dhp demonstrates potential as a stabilizing and biocompatible solvent for therapeutic proteins.
- These findings support the development of ILs for advanced protein-based drug formulations.
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