Ultra-high concentration low-viscosity subcutaneous antibody formulations using ionic liquids.

Area of Science:

• Biotechnology
• Pharmaceutical Sciences
• Materials Science

Background:

• Monoclonal antibodies (mAbs) are a major class of therapeutics for oncology, immunology, and neurology.
• Current subcutaneous mAb formulations face limitations due to protein-protein interactions, restricting concentrations to ~150 mg/ml.
• Developing high-concentration, low-viscosity, and stable subcutaneous mAb formulations is a critical unmet need.

Purpose of the Study:

• To investigate the use of ionic liquids (ILs) for formulating monoclonal antibodies at ultra-high concentrations.
• To assess the impact of ILs on antibody stability, viscosity, and bioavailability for subcutaneous administration.

Main Methods:

• Formulation of monoclonal antibodies (IgG) using specific ionic liquids (ILs).
• Characterization of IgG-IL formulations for concentration, viscosity, and stability at various temperatures.
• Evaluation of subcutaneous bioavailability of IgG-IL formulations compared to saline.

Main Results:

• Ionic liquids enabled the formulation of antibodies at concentrations exceeding 200 mg/ml.
• IgG-IL formulations maintained viscosity below the injectable threshold (<20 cP).
• Formulations demonstrated stability at room temperature and 37°C, with improved subcutaneous bioavailability.

Conclusions:

• Ionic liquids are effective in mitigating protein-protein interactions for ultra-high concentration mAb formulations.
• IL-based formulations offer a promising approach for stable, low-viscosity subcutaneous delivery of therapeutic antibodies.
• This technology addresses key challenges in mAb formulation, potentially enhancing therapeutic efficacy and patient convenience.