Ionic liquids and deep eutectic solvents for the stabilization of biopharmaceuticals: A review

Biopharmaceuticals have allowed the control of previously untreatable diseases. However, their low solubility and stability still hinder their application, transport, and storage. Hence, researchers have applied different compounds to preserve and enhance the delivery of biopharmaceuticals, such as ionic liquids (ILs) and deep eutectic solvents (DESs). Although the biopharmaceutical industry can employ various substances for enhancing formulations, their effect will change depending on the properties of the target biomolecule and environmental conditions. Hence, this review organized the current state-of-the-art on the application of ILs and DESs to stabilize biopharmaceuticals, considering the properties of the biomolecules, ILs, and DESs classes, concentration range, types of stability, and effect. We also provided a critical discussion regarding the potential utilization of ILs and DESs in pharmaceutical formulations, considering the restrictions in this field, as well as the advantages and drawbacks of these substances for medical applications. Overall, the most applied IL and DES classes for stabilizing biopharmaceuticals were cholinium-, imidazolium-, and ammonium-based, with cholinium ILs also employed to improve their delivery. Interestingly, dilute and concentrated ILs and DESs solutions presented similar results regarding the stabilization of biopharmaceuticals. With additional investigation, ILs and DESs have the potential to overcome current challenges in biopharmaceutical formulation.