Exploring the effects of excipients on complex coacervation

Area of Science:

• Biochemistry
• Materials Science
• Physical Chemistry

Background:

• Complex coacervation is a liquid-liquid phase separation driven by electrostatic interactions between oppositely charged polyelectrolytes.
• Its aqueous nature makes it suitable for biocompatible applications, with phase behavior traditionally studied based on charge stoichiometry, pH, and ionic strength.
• The phase equilibrium involves a balance of electrostatic attractions, excluded volume repulsions, and osmotic pressure.

Purpose of the Study:

• To investigate the potential of non-electrostatic excipients to modulate complex coacervation phase behavior.
• To explore the use of small molecule additives, commonly found in vaccine formulations, for tuning coacervate systems.
• To demonstrate the applicability of these modified coacervates in virus formulation.

Main Methods:

• Quantified the partitioning of small molecule excipients (sugars, amino acids, etc.) into the coacervate phase.
• Assessed the impact of these excipients on the destabilization of the phase separation.
• Integrated complex coacervation with these additives for virus formulation.

Main Results:

• Demonstrated that non-electrostatic excipients can partition into the coacervate phase.
• Showcased the ability of these excipients to alter solvent quality and osmotic pressure, thereby tuning phase behavior.
• Successfully combined modified complex coacervation with additives for virus formulation.

Conclusions:

• Complex coacervation phase behavior can be effectively tuned by incorporating non-electrostatic small molecule excipients.
• These findings offer a novel strategy for developing advanced biocompatible materials and formulations, particularly for vaccine and virus delivery systems.