Protein-Poly(amino acid) Complex Precipitation for High-Concentration Protein Formulation

A method for concentration of protein solutions is required for high-dosage protein formulation. Here, we present a precipitation-redissolution method by poly(amino acid) for proteins, including therapeutic enzymes, antibodies, and hormones. The proteins were fully precipitated by the addition of poly-l-lysine or poly-l-glutamic acid at low ionic strength, after which precipitate was dissolved at physiological ionic strength. The activities and secondary structures of redissolved proteins, especially antibodies, were almost identical to the native state. The precipitation-redissolution method is a simple and rapid technique for concentration of protein formulations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2248-2254, 2014