Biopharmaceuticals have allowed the successful treatment of illnesses with low recovery rates, such as cancers, autoimmune diseases, and metabolic disorders (Rasmussen et al., 2021). These compounds can include a wide variety of biomolecules based on amino acids and nucleic acids (Walsh, 2013), such as peptides, proteins, DNA, and RNA derivates. Their effectiveness has led to a growing demand, confirmed by a compound annual growth rate (CAGR) of 9.3% between 2016 and 2024, with an expected value of USD 405 billion by 2024 (Kim et al., 2022). However, due to their high prices and low stability outside of cold chains, most biopharmaceuticals are still inaccessible to low-income countries and communities (Ferrari, 2022). For example, many bioactive macromolecules are degraded or have poor absorption and bioavailability in vivo even when presenting pharmacological action in vitro (Manning et al., 2010). The inherent instability of biopharmaceuticals when outside their natural environment may cause limitations not only in their medical application, but also in their production, storage, and transportation. Therefore, the development of new formulations to stabilize and enhance the delivery of biopharmaceuticals can potentially expand their applications and improve their access in marginalized communities.

Several strategies have been applied to enhance the stability of biopharmaceuticals, such as the use of neoteric “green” solvents as additives in their formulations. For example, different classes of ionic liquids (ILs) and deep eutectic solvents (DESs) can be employed to improve the stability and delivery of biomolecules such as proteins and nucleic acids (Egorova et al., 2021; Veríssimo et al., 2022a). Thus, the development of novel green solvent formulations for biopharmaceuticals may lead to more efficient, sustainable, and environmentally friendly production and application of biologics (Dhiman et al., 2023).

To elucidate the advances in this field, this review will organize the state-of-the-art on the use of ILs and DESs for improving the stability and delivery of biopharmaceuticals. We will demonstrate the trends and knowledge gaps in this area and provide a perspective on the use of biocompatible ILs and DESs as additives in biopharmaceutical formulations. Firstly, we will present the main classes of biopharmaceuticals, their types of stability, and how to assess them. Then, we will discuss the properties of ILs and DESs, their biocompatibility, and their potential for application in biological systems. We will then demonstrate the effects of ILs and DESs on protein and nucleic acid biopharmaceuticals by examining their effects on individual biopharmaceuticals, followed by a debate regarding their overall use to stabilize and enhance the delivery of biotechnological medicines. As concluding remarks, we will provide our expert opinion concerning the trends and opportunities in the field, along with limitations and challenges to overcome.