ABSTRACT Concentrated protein formulations have garnered significant attention in both commercial and research domains due to their relevance in patient‐favored, subcutaneous administration. However, these formulations face challenges such as high viscosity and elevated potential for aggregation, primarily driven by intermolecular electrostatic and hydrophobic protein‐protein interactions (PPIs). Achieving an acceptable injectability profile (<20 cP) often necessitates the incorporation of excipients that mitigate PPIs through shielding effects. Current clinical formulations exhibit a narrow colloidal stability window, largely due to molecular changes under physical and thermal stress, whilst also suffering from suboptimal bioavailability (50%–85%). To address these limitations, we harness the utility of ionic liquids (ILs) that offer tunable charge and amphiphilicity profiles as a means to simplify and stabilize protein formulations. Herein, we synthesized biocompatible choline and organic acid‐based ILs and assessed their viscosity profiles with IgG antibody at both high (90 mg/mL) and ultra‐high (230 mg/mL) concentrations. Functional and structural stability assays conducted over 4 months at room temperature identified promising IL candidates for in vivo studies at both IgG concentrations. Through a multi‐tiered screening strategy, we generated thermally stable, ultra‐high concentration antibody solutions that achieved a five fold improvement in serum absorption of polyclonal IgG compared to their saline solutions.
Erdi et al. (2026) studied this question.