Ionic liquids as protein stabilizers for biological and biomedical applications: A review

Biotechnology has revolutionized science and health care by providing new biomolecules with biological and medical applications. However, the low stability of several life-saving bioproducts still hinders their transport, storage, and application. Hence, protein-based bioproducts instability and high costs are the main bottlenecks limiting access to biopharmaceuticals in low-income countries and communities. Aiming to improve the stability of protein-based products, researchers have studied ionic liquids (ILs) as protein stabilizers due to their unique properties and ability to enhance the solubility and stability of a wide range of biomolecules. Although different classes of ILs have the potential to improve protein stability, their effects are dependent on several variables, such as the complex and intrinsic properties of proteins, the nature and concentration of ILs, and environmental conditions (e.g., temperature, pH). For medical applications, the biocompatibility of ILs can also limit their biological use. Therefore, the current state-of-the-art on ILs applications for non-enzymatic protein stabilization was carefully analyzed and discussed, considering protein properties, ILs classes, and IL solutions concentrations. Lastly, a critical perspective regarding ILs applications as protein stabilizers was presented, highlighting the current lacunas in the field while guiding future studies to answer the existing paradigms.