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Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries

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Simultaneous Polymerization and Polypeptide Particle Production via Reactive Spray-Drying.

Lidija Glavas¹, Karin Odelius¹, Ann-Christine Albertsson¹

¹Fiber and Polymer Technology, School of Chemical Science and Engineering, KTH, Royal Institute of Technology , SE-100 44 Stockholm, Sweden.

Biomacromolecules

|July 23, 2016

Summary

A novel method enables rapid polypeptide particle production using in situ polymerization of N-carboxyanhydrides during spray-drying. This efficient process simplifies polypeptide synthesis for pharmaceutical applications.

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Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

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Area of Science:

Polymer Chemistry
Materials Science
Pharmaceutical Technology

Background:

Polypeptide particles are valuable in drug delivery.
Existing methods for polypeptide synthesis can be complex and time-consuming.
Spray-drying is a versatile technique for particle formation.

Purpose of the Study:

To develop a streamlined method for producing polypeptide particles.
To investigate the use of N-carboxyanhydride polymerization during spray-drying.
To assess the efficiency and robustness of the new synthetic pathway.

Main Methods:

Developed a rapid ring-opening polymerization of N-carboxyanhydrides using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an initiator.
Integrated polymerization with spray-drying by mixing monomer and initiator during atomization.
Utilized N-carboxyanhydride of l-glutamic acid benzyl ester (NCAGlu) as the monomer.

Main Results:

Achieved polymerization completion within 5 seconds.
Demonstrated high tolerance to impurities like amino acid salts and water.
Produced spherical polypeptide particles of approximately 1 μm in size.
Combined synthesis and particle formation into a single, straightforward process.

Conclusions:

The developed in situ polymerization during spray-drying is an efficient method for producing polypeptide particles.
This approach simplifies polypeptide particle fabrication, making it suitable for pharmaceutical applications.
The method enhances the utility of spray-drying for creating advanced polypeptide-based materials.