Ionic liquids as stabilisers of therapeutic protein formulations: a review of insulin and monoclonal antibodies

Therapeutic proteins such as insulin and monoclonal antibodies (mAbs) have become an essential part of the modern healthcare system and play a crucial role in the treatment of various diseases including cancer and autoimmune disorders. However, their long-term stability is a significant concern, affecting efficacy, shelf-life, and safety. Ionic liquids (ILs) have emerged as promising additives to enhance protein stability and address the aforementioned issues. Indeed, recent studies indicate that biocompatible ILs, particularly choline-based ILs, have significant potential to improve stability while preserving proteins’ functionality. For instance, choline valinate has been shown to increase the melting temperature of insulin by almost 13 °C (Judy and Kishore Biochimie 207:20-32, 2023), while choline dihydrogen phosphate has increased the melting temperature of trastuzumab by over 21 °C (Reslan et al. Chem Commun 54:10622-10625, 2018). However, it is worth noting that the use of some ILs introduces a complex trade-off: while they can increase thermal stability, they may also promote protein unfolding, thereby reducing conformational stability. Moreover, selecting the most suitable IL and its optimal concentration is challenging, as different protein formulations may exhibit varying effects. This review provides a comprehensive overview of the existing literature on ILs as stabilisers for insulin and mAbs, documenting specific IL-protein combinations and conditions to identify potential future stabilising agents for biologics in general.