Abstract
Ionic liquids (ILs) have recently emerged as versatile solvents and additives in the field of biotechnology, particularly as stabilizers of proteins and enzymes. Of interest to the biotechnology industry is the formulation of stable biopharmaceuticals, therapeutic proteins, and vaccines which have revolutionized the treatment of many diseases including debilitating conditions such as cancers and auto-immune diseases. The stabilization of therapeutic proteins is typically achieved using additives that prevent unfolding and aggregation of these proteins during manufacture, transport, and long-term storage. To determine if ILs could be used in the formulation of stable therapeutic proteins, a thorough understanding of the effects of ILs on protein stability is needed, as well as understanding the toxicity of ILs on humans, and other considerations for formulation development such as viscosity and osmolality. In this review, we summarize recent developments on the stabilization of proteins and enzymes using ILs, with emphasis on identifying biocompatible ILs that may be suitable for the formulation of stable biopharmaceuticals in the future.
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Abbreviations
- ILs:
-
Ionic liquids
- PIL:
-
Protic ionic liquid
- AIL:
-
Aprotic ionic liquid
- EAN:
-
Ethylammonium nitrate
- DHP:
-
Dihydrogen phosphate
- Chol:
-
Choline
- BMIM:
-
1-Butyl-3-methyilimidazolium
- EMIM:
-
1-Ethyl-3-methylimidazolium
- PMIM:
-
1-Methyl-3-propylimidazolium
- HMIM:
-
1-Hexyl-3-methylimidazolium
- MMIM:
-
1,3-Dimethylimidazolium
- SCN:
-
Thiocyanate
- Cyt C:
-
Cytochrome complex
- BSA:
-
Bovine serum albumin
- rPa:
-
Recombinant plasminogen activator
- MDEG:
-
2(2-Methoxyethoxy)-ethyl
- HexSO4 :
-
Hexylsulfate
- Tos:
-
Tosylate
- OH-EMIM:
-
1-(2-Hydroxyethyl)-3-methylimidazolium
- OH-PMIM:
-
1-(3-Hydroxypropyl)-3-methylimidazolium
- OH-HMIM:
-
1-(6-Hydroxyhexyl)-3-methylimidazolium
- BF4 :
-
Tetrafluoroborate
- CT:
-
α-Chymotrypsinogen
- BzMIM:
-
1-Benzyl-3-methylimidazolium
- TEAA:
-
Triethylammonium acetate
- TEAP:
-
Triethylammonium phosphate
- TBPBr:
-
Tetrabutylphosphonium bromide
- Ac:
-
Acetate
- Cit:
-
Citrate
- rHIL-2:
-
Recombinant human interleukin-2
- TMA:
-
Trimethyl acetate
- Lac:
-
Lactate
- Prop:
-
Propionate
- Hex:
-
Hexanoate
- DMP:
-
Dimethyl phosphate
- TFMS:
-
Trifluoromethane sulfonate
- TF2N:
-
Bis(trifluoromethylsulfonyl)amide
- Glu:
-
Glutarate
- GuHCl:
-
Guanidine hydrochloride
- mAb:
-
Monoclonal antibody
- EGFR:
-
Epidermal growth factor receptor
- MD:
-
Molecular dynamics
- DBP:
-
Dibutyl phosphate
- BEH:
-
Bis(2-ethylhexyl) phosphate
- TMP:
-
Bis(2,4,4-trimethylpentyl) phosphinate
- DEP:
-
O,O′-diethyl dithiophosphate
- EOOEMIM:
-
3-Methyl-1-(ethoxycarbonylmethyl)imidazolium
- [EOOEMPy][C12SO4]:
-
3-Methyl-1-(ethoxycarbonylmethyl)pyrrolidinium
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Mouhamad Reslan declares that he has no conflict of interest. Veysel Kayser declares that he has no conflict of interest.
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This article is part of a Special Issue on ‘Ionic Liquids and Biomolecules’ edited by Antonio Benedetto and Hans-Joachim Galla.
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Reslan, M., Kayser, V. Ionic liquids as biocompatible stabilizers of proteins. Biophys Rev 10, 781–793 (2018). https://doi.org/10.1007/s12551-018-0407-6
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DOI: https://doi.org/10.1007/s12551-018-0407-6