Biomacromolecules, Vol.17, No.9, 2930-2936, 2016
Simultaneous Polymerization and Polypeptide Particle Production via Reactive Spray-Drying
A method for producing polypeptide particles via in situ polymerization of N-carboxyanhydrides during spray-drying has been developed. This method was enabled by the development of a fast and robust synthetic pathway to polypeptides using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an initiator for the ring-opening polymerization of N-carboxyanhydrides. The polymerizations finished within 5 s and proved to be very tolerant toward impurities such as amino acid salts and water. The formed particles were prepared by mixing the monomer, N-carboxyanhydride of L-glutamic acid benzyl ester (NCA(Glu)) and the initiator (DBU) during the atomization process in the spray-dryer and were spherical with a size of similar to 1 um. This method combines two steps; making it a straightforward process that facilitates the production of polypeptide particles. Hence, it furthers the use of spray-drying and polypeptide particles in the pharmaceutical industry.