Factors affecting the physical stability (aggregation) of peptide therapeutics

Area of Science:

• Biopharmaceutical development
• Protein aggregation science

Background:

• Biological therapeutics are increasingly prevalent.
• Physical stability is a major challenge in biologic development, production, and formulation.
• Self-association into aggregates limits the therapeutic use of many biologics.

Purpose of the Study:

• To review factors influencing the physical stability of therapeutic peptides.
• To discuss the structures and formation mechanisms of peptide aggregates.

Main Methods:

• Literature review of factors affecting peptide physical stability.
• Discussion of intrinsic and external factors influencing peptide aggregation.
• Overview of aggregate structures and formation mechanisms.

Main Results:

• Numerous factors, including sequence, concentration, pH, charge, excipients, degradation, surfaces, impurities, pressure, temperature, agitation, and lyophilization, impact peptide stability.
• Both amorphous and fibrillar aggregates can form, limiting therapeutic application.
• Mechanisms of aggregate formation are complex and influenced by multiple parameters.

Conclusions:

• Understanding the factors affecting peptide physical stability is crucial for successful biopharmaceutical development.
• Mitigating self-association and aggregation is key to improving the utility of peptide-based therapeutics.