Phosphatidylcholine-Polysorbate 20-Based Mixed Micelles: A New Option to Prevent Protein Aggregation?

Area of Science:

• Biopharmaceutical formulation and stabilization
• Protein and antibody drug product development
• Excipient science and drug delivery systems

Background:

• Surfactants like polysorbates (PS) are crucial for biopharmaceutical stability, preventing protein denaturation and aggregation.
• Polysorbates 20 and 80 are widely used, but alternatives are sought to mitigate potential issues.
• Mixed micelles (MMs) of phospholipids (PL) and PS20 present a novel strategy for protein stabilization.

Purpose of the Study:

• To explore mixed micelles (MMs) of phospholipids (PL) and polysorbate 20 (PS20) as a novel stabilization strategy for biopharmaceuticals.
• To investigate the potential of reducing polysorbate content in protein formulations through partial substitution with phospholipids.
• To assess the efficacy of PL/PS20 MMs in stabilizing antibody solutions.

Main Methods:

• Formulation of mixed micelles (MMs) using direct dispersion with an optimized two-step heating process.
• Characterization of MM formation using transmission electron microscopy and dynamic light scattering.
• Stability assessment of model proteins (bovine serum albumin) and a monoclonal antibody under agitation stress using visual inspection, turbidity, particle analysis, and size-exclusion chromatography.

Main Results:

• Stable MM solutions were formed with varying PS20/PL ratios and high total surfactant concentrations (up to 50 mg·mL⁻¹), exceeding typical formulation limits.
• The PL/PS20 micellar system demonstrated successful formation and stability.
• Agitation studies showed that PL/PS20 MMs provided a protective effect comparable to PS20 alone for both model proteins and the monoclonal antibody.

Conclusions:

• Mixed micelles (MMs) composed of phospholipids and polysorbate 20 are effective in stabilizing biologics, including monoclonal antibodies.
• This study demonstrates for the first time the successful application of MMs for stabilizing antibody solutions.
• The PL/PS20 micellar system offers a promising alternative excipient strategy for biopharmaceutical formulations.