High Concentration Antibody Formulations Enabled via Thermostable Ionic Liquids.

Area of Science:

• Biochemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Concentrated protein formulations are crucial for subcutaneous drug delivery but face challenges like high viscosity and aggregation.
• Current formulations have limited colloidal stability and suboptimal bioavailability (50%-85%).
• Protein-protein interactions (PPIs) driven by electrostatic and hydrophobic forces contribute to these formulation issues.

Purpose of the Study:

• To explore the use of ionic liquids (ILs) as stabilizing excipients for concentrated protein formulations.
• To synthesize and evaluate biocompatible ILs for mitigating PPIs and improving formulation properties.
• To enhance the stability, injectability, and bioavailability of high and ultra-high concentration protein solutions.

Main Methods:

• Synthesized biocompatible choline and organic acid-based ionic liquids (ILs).
• Assessed viscosity profiles of IgG antibody formulations (90 mg/mL and 230 mg/mL) with ILs.
• Conducted functional and structural stability assays over 4 months at room temperature.
• Evaluated serum absorption of polyclonal IgG in IL-stabilized solutions compared to saline.

Main Results:

• Identified promising IL candidates for stabilizing IgG at high and ultra-high concentrations.
• Generated thermally stable, ultra-high concentration antibody solutions.
• Achieved a five-fold improvement in serum absorption of polyclonal IgG compared to saline solutions.
• Demonstrated ILs' ability to mitigate protein-protein interactions and improve formulation characteristics.

Conclusions:

• Biocompatible ionic liquids offer a promising strategy for simplifying and stabilizing concentrated protein formulations.
• ILs can enhance the injectability and bioavailability of subcutaneous protein therapeutics.
• This approach holds potential for developing advanced drug delivery systems with improved patient compliance and therapeutic efficacy.