Aggregative protein-polyelectrolyte complex for high-concentration formulation of protein drugs.
Aggregative protein-polyelectrolyte complex (PPC) has been proposed as a concentrated state of protein with a great potential for biopharmaceutical application. In this review article, we introduce a unique concentration method of protein formulation using PPC for a dozen types of pharmaceutical antibodies, hormones, and enzymes. Aggregative PPC can be obtained only by mixing poly(amino acid)s with proteins under low salt concentration conditions at an ambient temperature. The aggregative PPC is in a stabilized state against shaking, heating, and oxidation. More importantly, the aggregative PPC can be fully redissolved by the addition of physiological saline without denaturation and activity loss for many proteins. In addition, the general toxicity and pharmacokinetic profiles of the aggregative PPC are identical to those of the control antibody formulation. Thus, the protein formulation produced by aggregative PPC would be applicable for biomedical use as a kind of concentrated-state protein.
Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
Takaaki
T
Kurinomaru
Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: shiraki@bk.tsukuba.ac.jp.
Kentaro
K
Shiraki
D004339:Drug Compounding; D006801:Humans; D000071228:Polyelectrolytes / Q000737:chemistry*; D066329:Protein Aggregates; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use*; D014783:Viscosity
D000071228:Polyelectrolytes; D066329:Protein Aggregates; D011506:Proteins
Concentration; Precipitation; Protein–polyelectrolyte complex