Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 1477 word(s) 1477 2021-09-26 05:45:13 |
2 update references and layout Meta information modification 1477 2021-09-30 04:42:20 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Correia, D. Ionic Liquid-Based Materials, Biomedical Applications. Encyclopedia. Available online: (accessed on 15 June 2024).
Correia D. Ionic Liquid-Based Materials, Biomedical Applications. Encyclopedia. Available at: Accessed June 15, 2024.
Correia, Daniela. "Ionic Liquid-Based Materials, Biomedical Applications" Encyclopedia, (accessed June 15, 2024).
Correia, D. (2021, September 29). Ionic Liquid-Based Materials, Biomedical Applications. In Encyclopedia.
Correia, Daniela. "Ionic Liquid-Based Materials, Biomedical Applications." Encyclopedia. Web. 29 September, 2021.
Ionic Liquid-Based Materials, Biomedical Applications

Ionic liquids (ILs) are being applied in a wide range of areas such as sensors and actuators. The increasing attention devoted to ILs is based on their unique properties and possible combination of different cations and anions, allowing the development of materials with specific functionalities and requirements for applications. In recent years, ILs have also been gaining attention in the biomedical field, where they allow important advances in novel pharmaceutics and medical strategies. 

biomedical applications ionic liquids IL-polymer based materials

1. Introduction

ILs are commonly defined as salts composed of organic cations and organic/inorganic anions with low melting temperatures [1]. They can be synthesized with a large number of specific functionalities [1][2]. Some of the interesting physical-chemical properties of ILs include tailored viscosity [3][4], melting temperature [5], solubility, stability at high temperatures, and surface activity [6], which are important for developing specific materials for biomedical applications. It is noteworthy that deep eutectic solvents (DESs), formed by the mixture of a hydrogen bond acceptor and a donor, show similar properties to ILs and have been also used for biomedical applications. However, DESs have been replaced by ILs in the most recent studies [7][8][9].

ILs are mainly derived from petroleum-based constituents such as imidazolium and pyridinium and can display toxicity and release hazardous decomposition products under certain conditions [10][11][12][13]. This has led to their “green” nature being questioned over the past few years [14][15]. Due to the strong socioeconomic impact of ILs and the doubts around their “green” nature, the synthesis of biocompatible ILs has gained special attention, expanding their applicability in different fields, particularly in the biomedical area.

The most effective strategy for the development of biocompatible compounds relies on the use of choline as the cationic moiety in the structure. It has been shown that the use of this component as cation allows the development of biocompatible ILs with biodegradability and very low toxicity [16]; nonetheless, it has been also reported [17] that more detailed toxicological tests with different organisms are necessary to truly determine the biocompatibility of the choline amino acid based ILs. The combination of cholinium cations with other compounds such as amino acids, artificial sweeteners, or carboxylic acids such as anions has been performed in recent years [18]. Besides the large attention devoted in cholinium based ILs and the intensive research in this field, some biocompatible alternatives to cholinium as cation for biocompatible ILs synthesis have received consideration.

The combination of ILs with different polymer-based materials has been also explored in recent years. For the preparation of biomaterials, ILs can play different roles by assisting or participating in the formation of the materials through polymer dissolution or polymer regeneration.  IL/biopolymer hybrid materials are also emerging as biomaterials in biomedical applications [19]. Due to the large number of available combinations of ILs, and based on their intrinsic properties, they are being successfully implemented in a variety of applications in this field, such as biodegradable composite biomaterials [20][21][22], or pharmaceuticals [19][23], among others.

2. Biomedical Applications of Ionic Liquids-Based Materials

ILs have been commonly employed in the development of biomaterials, in particular in combination with natural and synthetic polymers for different biomedical areas, including drug delivery, cancer therapy, tissue engineering, antimicrobial and antifungal agents, and biosensing. As an example, in the area of drug delivery, ILs have been used either to develop delivery systems and pharmaceutical formulations or to functionalize biopolymers ( Figure 1 ).


Figure 1. Applications of ILs in drug delivery systems design and development (APIs: active pharmaceuticals ingredients). Reprinted with permission from [24].

Table 1 reports the main works using IL-based materials for drug delivery applications, presenting the used materials, the target application, as well as the main obtained results.

Materials Ionic Liquids (ILs) Biomedical Property Ref.
Chitosan [Ch][Cl] Electrical and pH-sensitive drug delivery [25]
Chitin [C2mim][Ac] Topical release drug delivery [26]
[Bmim][HSO4] Sustained drug release application [27]
Choline acrylate
Choline chloride-thiourea
Cellulose/Chitosan/Keratin [Bmim][Cl] Bandage to treat chronic and ulcerous wounds [28]
Cellulose/Fe3O4 NPs/Heparin [Emim][Ac] Magnetically responsive drug delivery [29]
Locust bean gum [Bmim][Cl] Potential drug delivery system [30]
Active pharmaceutical ingredient/grafted-PLLA Choline chloride Potential drug delivery system [31]
di(2-hydroxyethyl)dimethyl ammonium bromide
Active pharmaceutical ingredient/grafted-PLLA 2-hydroxyethyl triethyl ammonium bromide Drug delivery system [32]
2-hydroxyethyl tributyl ammonium bromide
di(2-hydroxyethyl)dibutyl ammonium bromide
tris(2-hydroxyethyl)butyl ammonium bromide
pH-sensitive polymer/montmorillonite (MMT) 3-methyl-1-[2-(2-methyl-acryloxy)ethyl]imidazolium chloride Colon Specific Drug Delivery System [33]
Cellulose/PNIPAAm [Bmim][Cl] Temperature and pH-sensitive drug delivery [34]

One of the most attractive characteristics of ILs is the fact that they can be dissolved in a wide range of solvents, including water, which makes them suitable for biomedical applications. Aqueous solutions of certain ILs have been indeed reported to possess potent antimicrobial activity [35][36]. Although dissolved ILs are not considered true ILs since they no longer consist exclusively of parent ions [37], this may indicate that the mechanism of action is due to one or both ions, both being able to possess inherent antimicrobial activity [38].


3. Main Conclusions and Future Trends

Due to their specific properties, ILs have been explored for a wide range of applications, of which biomedical applications are of particular interest and current activity. The large possible combinations of different cations and anions allow the development of a high and vast number of ILs with specific and tailored properties. Particularly for biomedical applications, the development of biocompatible and non-toxic ILs has been essential. Currently, the most commonly used ILs remain protein-derived amino-acids cations and anions and choline cations, but also other types are emerging in fields such as cancer treatment, biocides, or biosensing.

Besides the increasing interest devoted to ILs for different fields and application areas, the most common use of ILs is as green solvents for a wide range of polymers and other materials. Nevertheless, their combination with polymers matrixes to form IL/polymer-based hybrid materials is rapidly getting recognition in areas such as sensors, actuators, and tissue engineering where they have demonstrated an outstanding potential. Particularly for biomedical applications, and based on their different actuation possibilities, ILs are emerging as highly valuable candidates. Novel studies are demonstrating, for instance, the potential of ILs in drug delivery systems with photo-, temperature- or pH-sensitive drug release behavior. For tissue engineering, ILs have been employed as polymer solvents, and have been combined with polymers to develop a wide variety of responsive and functional materials, including films, fibers, spheres, membranes, and hydrogels. These early works make also evident that significant efforts to understand these systems are still necessary. For instance, the IL stability and release, in the case of drug delivery systems, needs to be better understood, while a lack of studies exists concerning the influence of the IL on the cell behavior of a larger variety of cells, namely their adhesion, proliferation, and differentiation. The effect of the ionic charges in the cells is also absent in many studies, reflecting the necessity of new works on the dynamics of the effect of the ILs ionic charges on cells.

The demonstration that certain ILs present less cytotoxicity against healthy cells than against cancer cells supports the potential of ILs to be used in the development of novel strategies for cancer therapies. Also highly related, the strong potential of ILs as antimicrobial and antifungal agents in biomedical applications, such as wound dressing, has been also demonstrated. In this field of applicability, advances are necessary to evaluate the cytotoxicity towards different cell lines determining the window of concentrations that are safe using. Finally, ILs have been also explored in the field of biomedical sensing and biosensing through the development of sensors able to recognize temperature and force variations, as well as to identify biomolecules, proteins, and pharmaceuticals, among others.

Despite the growing number of studies concerning the use of ILs in different areas of the biomedical field, strong efforts concerning the ILs toxicity, stability over time, and degradability as well the IL degradation products should be addressed deeply. Additionally, it is noteworthy that currently, a high number of studies report the use of ILs as solvents during preparation of materials, with still a limited number of studies existing on IL/polymer-based materials for biomedical applications. In this scope, the combination ILs with other materials allows them to confer interesting functional responses to the systems, including optical, catalytic, or shape memory. As an example, the exploration of the magnetic properties of ILs and magnetic ILs/polymer materials for tissue regeneration holds interesting potential. Different studies reports that the magnetic field can promote cell proliferation and differentiation mostly based on magnetic nanoparticles, which are toxic in certain concentrations. In this regard, magnetic ILs are of great interest due to the possibility of developing magnetic-particle-free magnetically responsive hybrid materials. Thus, IL and their tailorable properties as well as their rich synergetic effect in their combinations with polymers and related materials holds great promise as a next generation of smart and multifunctional materials for biomedical and biotechnological applications.


  1. Daniela Maria Correia; Liliana Fernandes; Pedro Martins; Clara García-Astrain; Carlos Miguel Costa; Javier Reguera; Senentxu Lanceros‐Méndez; Ionic Liquid–Polymer Composites: A New Platform for Multifunctional Applications. Advanced Functional Materials 2020, 30, 1909736, 10.1002/adfm.201909736.
  2. Carolina Cruz; Alina Ciach; Phase Transitions and Electrochemical Properties of Ionic Liquids and Ionic Liquid—Solvent Mixtures. Molecules 2021, 26, 3668, 10.3390/molecules26123668.
  3. I.M. Marrucho; Luis Branco; Luis Paulo Rebelo; Ionic Liquids in Pharmaceutical Applications. Annual Review of Chemical and Biomolecular Engineering 2014, 5, 527-546, 10.1146/annurev-chembioeng-060713-040024.
  4. Guangren Yu; Dachuan Zhao; Lu Wen; Shendu Yang; Xiaochun Chen; Viscosity of ionic liquids: Database, observation, and quantitative structure-property relationship analysis. AIChE Journal 2011, 58, 2885-2899, 10.1002/aic.12786.
  5. Fangyou Yan; Shuqian Xia; Qiang Wang; Zhen Yang; Peisheng Ma; Predicting the melting points of ionic liquids by the Quantitative Structure Property Relationship method using a topological index. The Journal of Chemical Thermodynamics 2013, 62, 196-200, 10.1016/j.jct.2013.03.016.
  6. Haibo Zhang; Xiaohai Zhou; Jinfeng Dong; Gaoyong Zhang; Cunxin Wang; A novel family of green ionic liquids with surface activities. Science China Chemistry 2007, 50, 238-242, 10.1007/s11426-007-0024-x.
  7. Fatemeh Soltanmohammadi; Abolghasem Jouyban; Ali Shayanfar; New aspects of deep eutectic solvents: extraction, pharmaceutical applications, as catalyst and gas capture. Chemical Papers 2020, 75, 439-453, 10.1007/s11696-020-01316-w.
  8. Shahram Emami; Ali Shayanfar; Deep eutectic solvents for pharmaceutical formulation and drug delivery applications. Pharmaceutical Development and Technology 2020, 25, 779-796, 10.1080/10837450.2020.1735414.
  9. Mohamad Hamdi Zainal-Abidin; Maan Hayyan; Won Fen Wong; Hydrophobic deep eutectic solvents: Current progress and future directions. Journal of Industrial and Engineering Chemistry 2021, 97, 142-162, 10.1016/j.jiec.2021.03.011.
  10. Marija Petkovic; Kenneth R. Seddon; Luis Paulo N. Rebelo; Cristina Silva Pereira; ChemInform Abstract: Ionic Liquids: A Pathway to Environmental Acceptability. ChemInform 2011, 42, 1383-1403, 10.1002/chin.201127270.
  11. Deborah Coleman; Nicholas Gathergood; Biodegradation studies of ionic liquids. Chemical Society Reviews 2010, 39, 600-637, 10.1039/b817717c.
  12. Richard P. Swatloski; John Holbrey; Robin D. Rogers; Ionic liquids are not always green: hydrolysis of 1-butyl-3-methylimidazolium hexafluorophosphate. Green Chemistry 2003, 5, 361-363, 10.1039/b304400a.
  13. Marianne Matzke; Stefan Stolte; Karen Thiele; Tanja Juffernholz; Jürgen Arning; Johannes Ranke; Urs Welz-Biermann; Bernd Jastorff; The influence of anion species on the toxicity of 1-alkyl-3-methylimidazolium ionic liquids observed in an (eco)toxicological test battery. Green Chemistry 2007, 9, 1198-1207, 10.1039/b705795d.
  14. Dongbin Zhao; Yongcheng Liao; Ziding Zhang; Toxicity of Ionic Liquids. CLEAN - Soil, Air, Water 2007, 35, 42-48, 10.1002/clen.200600015.
  15. Thi Phuong Thuy Pham; Chul-Woong Cho; Yeoung-Sang Yun; Environmental fate and toxicity of ionic liquids: A review. Water Research 2010, 44, 352-372, 10.1016/j.watres.2009.09.030.
  16. J. I. Santos; A. M. M. Gonçalves; J. L. Pereira; B. F. H. T. Figueiredo; Francisca Silva; Joao Coutinho; S. P. M. Ventura; Fernando J. M. Gonçalves; Environmental safety of cholinium-based ionic liquids: assessing structure–ecotoxicity relationships. Green Chemistry 2015, 17, 4657-4668, 10.1039/c5gc01129a.
  17. Xue-Dan Hou; Qiu-Ping Liu; Thomas Smith; Ning Li; Min-Hua Zong; Evaluation of Toxicity and Biodegradability of Cholinium Amino Acids Ionic Liquids. PLOS ONE 2013, 8, e59145, 10.1371/journal.pone.0059145.
  18. Balu Gadilohar; Ganapati Shankarling; Choline based ionic liquids and their applications in organic transformation. Journal of Molecular Liquids 2017, 227, 234-261, 10.1016/j.molliq.2016.11.136.
  19. Jing Chen; Fengwei Xie; Xiaoxi Li; Ling Chen; Ionic liquids for the preparation of biopolymer materials for drug/gene delivery: a review. Green Chem. 2018, 20, 4169-4200, 10.1039/c8gc01120f.
  20. Julia L. Shamshina; Oleksandra Zavgorodnya; Robin D. Rogers; Advances in Processing Chitin as a Promising Biomaterial from Ionic Liquids. Blue Biotechnology 2018, 168, 177-198, 10.1007/10_2018_63.
  21. Simone S. Silva; João F. Mano; Rui L. Reis; Ionic liquids in the processing and chemical modification of chitin and chitosan for biomedical applications. Green Chemistry 2016, 19, 1208-1220, 10.1039/c6gc02827f.
  22. Hamayoun Mahmood; Muhammad Moniruzzaman; Suzana Yusup; Tom Welton; Ionic liquids assisted processing of renewable resources for the fabrication of biodegradable composite materials. Green Chemistry 2017, 19, 2051-2075, 10.1039/c7gc00318h.
  23. Noorul Adawiyah; Muhammad Moniruzzaman; Siti Hawatulaila; Masahiro Goto; Ionic liquids as a potential tool for drug delivery systems. MedChemComm 2016, 7, 1881-1897, 10.1039/c6md00358c.
  24. Julia L Shamshina; Patrick S Barber; Robin D Rogers; Ionic liquids in drug delivery. Expert Opinion on Drug Delivery 2013, 10, 1367-1381, 10.1517/17425247.2013.808185.
  25. A. M. A. Dias; A. R. Cortez; M. M. Barsan; J. B. Santos; C. M. A. Brett; H. C. de Sousa; Development of Greener Multi-Responsive Chitosan Biomaterials Doped with Biocompatible Ammonium Ionic Liquids. ACS Sustainable Chemistry & Engineering 2013, 1, 1480-1492, 10.1021/sc4002577.
  26. Catherine King; Julia L. Shamshina; Gabriela Gurau; Paula Berton; Nur Farahnadiah Abdul Faruk Khan; Robin D. Rogers; A platform for more sustainable chitin films from an ionic liquid process. Green Chemistry 2016, 19, 117-126, 10.1039/c6gc02201d.
  27. Chandrakant Mukesh; Dibyendu Mondal; Mukesh Sharma; Kamalesh Prasad; Choline chloride–thiourea, a deep eutectic solvent for the production of chitin nanofibers. Carbohydrate Polymers 2014, 103, 466-471, 10.1016/j.carbpol.2013.12.082.
  28. Chieu D. Tran; Tamutsiwa M. Mututuvari; Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release. Langmuir 2015, 31, 1516-1526, 10.1021/la5034367.
  29. Lijuan Hou; W. M. Ranodhi N. Udangawa; Anirudh Pochiraju; Wenjun Dong; Yingying Zheng; Robert J. Linhardt; Trevor J. Simmons; Synthesis of Heparin-Immobilized, Magnetically Addressable Cellulose Nanofibers for Biomedical Applications. ACS Biomaterials Science & Engineering 2016, 2, 1905-1913, 10.1021/acsbiomaterials.6b00273.
  30. Márcia G. Ventura; Ana Inês Paninho; Ana V. M. Nunes; Isabel M. Fonseca; Luís C. Branco; Biocompatible locust bean gum mesoporous matrices prepared by ionic liquids and a scCO2 sustainable system. RSC Advances 2015, 5, 107700-107706, 10.1039/c5ra17314k.
  31. Mohammed Halayqa; Maciej Zawadzki; Urszula Domańska; Andrzej Plichta; API-ammonium ionic liquid – Polymer compounds as a potential tool for delivery systems. Journal of Molecular Liquids 2017, 248, 972-980, 10.1016/j.molliq.2017.10.136.
  32. Mohammed Halayqa; Maciej Zawadzki; Urszula Domańska; Andrzej Plichta; Polymer – Ionic liquid – Pharmaceutical conjugates as drug delivery systems. Journal of Molecular Structure 2018, 1180, 573-584, 10.1016/j.molstruc.2018.12.023.
  33. Mehrdad Mahkam; Abdolrahim Abbaszad Rafi; Leila Mohammadzadeh Gheshlaghi; Preparation of novel pH-sensitive nanocomposites based on ionic-liquid modified montmorillonite for colon specific drug delivery system. Polymer Composites 2014, 37, 182-187, 10.1002/pc.23169.
  34. Daoben Hua; Jianlin Jiang; Liangju Kuang; Jing Jiang; Wan Zheng; Hongjun Liang; Smart Chitosan-Based Stimuli-Responsive Nanocarriers for the Controlled Delivery of Hydrophobic Pharmaceuticals. Macromolecules 2011, 44, 1298-1302, 10.1021/ma102568p.
  35. Louise Carson; Peter K. W. Chau; Martyn J. Earle; Manuela A. Gilea; Brendan F. Gilmore; Sean P. Gorman; Maureen T. McCann; Kenneth R. Seddon; Antibiofilm activities of 1-alkyl-3-methylimidazolium chloride ionic liquids. Green Chemistry 2009, 11, 492-497, 10.1039/b821842k.
  36. Alessandro Busetti; Deborah E. Crawford; Martyn J. Earle; Manuela A. Gilea; Brendan F. Gilmore; Sean P. Gorman; Garry Laverty; Andrew F. Lowry; Martin McLaughlin; Kenneth R. Seddon; et al. Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chemistry 2010, 12, 420-425, 10.1039/b919872e.
  37. Freemantle, Michael; An introduction to ionic liquids. Choice Reviews Online 2010, 47, 47-6874, 10.5860/choice.47-6874.
  38. Brendan F. Gilmore; Gavin P. Andrews; Gabor Borberly; Martyn J. Earle; Manuela A. Gilea; Sean P. Gorman; Andrew F. Lowry; Martin McLaughlin; Kenneth R. Seddon; Enhanced antimicrobial activities of 1-alkyl-3-methyl imidazolium ionic liquids based on silver or copper containing anions. New Journal of Chemistry 2013, 37, 873-876, 10.1039/c3nj40759d.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 489
Revisions: 2 times (View History)
Update Date: 30 Sep 2021
Video Production Service