Toward Quantitative End-Group Fidelity in the Synthesis of High Molecular Weight Polysarcosine.

Summary

The authors benchmarked synthesis routes for high molecular weight polysarcosine and quantified end-group fidelity using ion-exchange chromatography, isolating and identifying side products by mass spectrometry. These data provide mechanistic insight and practical routes to heterotelechelic pSar with higher end-group integrity, advancing PEG-alternative excipients for pharma and cosmetics.

Key Findings

• Compared current methods for controlled synthesis of polysarcosine over a broad molecular weight range.
• Quantified end-group fidelity using ion-exchange chromatography and isolated impurities.
• Mass spectrometry identified side products, providing mechanistic insight to improve heterotelechelic pSar integrity.

Clinical Implications

While preclinical, higher-fidelity polysarcosine could reduce immunogenicity risks related to PEG and improve consistency of topical, injectable, and implantable formulations used in dermatology and aesthetic medicine.

Limitations

• Laboratory-scale evaluation without in vivo or clinical testing of immunogenicity.
• Process scalability and GMP implementation details are not reported.

Future Directions

Translate high-fidelity pSar synthesis to GMP processes, compare immunogenicity and performance against PEG in relevant preclinical models, and validate in topical and parenteral formulations.