High Concentration Antibody Formulations Enabled via Thermostable Ionic Liquids.

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.