Liquid droplets of protein–polyelectrolyte complexes (PPCs) have been developed as a new candidate for stabilization and concentration of protein drugs. However, it remains unclear whether additives affect the precipitation and redissolution yields of PPCs. In the present study, we investigated the PPC formation of human immunoglobulin G (IgG) and poly-L-glutamic acid (polyE) in the presence of various additives that have diverse effects, such as protein stabilization. Alcohols, including ethanol, successfully increased the PPC precipitation yield to over 90%, and the PPCs formed were completely redissolved at physiological ionic strength. However, poly(ethylene glycol), sugars, and amino acids did not improve the precipitation and redissolution yields of PPCs over those observed when no additives were included. Circular dichroism spectrometry showed that the secondary structure of polyE as well as electrostatic interactions play important roles in increasing the PPC precipitation yield when ethanol is used as an additive. The maximum concentration of IgG reached 100 mg/ml with the use of ethanol, which was 15% higher efficiency of the protein yield after precipitation and redissolution than that in the absence of additives. Thus, the addition of a small amount of ethanol is effective for the concentration and stabilization of precipitated PPCs containing IgG formulations.
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14 February 2019
Research Article|
February 12 2019
Effect of additives on liquid droplet of protein–polyelectrolyte complex for high-concentration formulations
Masahiro Mimura;
Masahiro Mimura
1
Faculty of Pure and Applied Sciences, University of Tsukuba
, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan
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Keisuke Tsumura;
Keisuke Tsumura
1
Faculty of Pure and Applied Sciences, University of Tsukuba
, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan
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Ayumi Matsuda;
Ayumi Matsuda
1
Faculty of Pure and Applied Sciences, University of Tsukuba
, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan
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Naoki Akatsuka;
Naoki Akatsuka
2
Research and Development Center, Terumo Corporation
, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan
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Kentaro Shiraki
Kentaro Shiraki
a)
1
Faculty of Pure and Applied Sciences, University of Tsukuba
, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan
a)Author to whom correspondence should be addressed: [email protected]. Tel.: +81-29-853-5306. Fax: +81-29-853-5215.
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Masahiro Mimura
1
Keisuke Tsumura
1
Ayumi Matsuda
1
Naoki Akatsuka
2
Kentaro Shiraki
1,a)
1
Faculty of Pure and Applied Sciences, University of Tsukuba
, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan
2
Research and Development Center, Terumo Corporation
, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan
a)Author to whom correspondence should be addressed: [email protected]. Tel.: +81-29-853-5306. Fax: +81-29-853-5215.
J. Chem. Phys. 150, 064903 (2019)
Article history
Received:
September 26 2018
Accepted:
January 21 2019
Citation
Masahiro Mimura, Keisuke Tsumura, Ayumi Matsuda, Naoki Akatsuka, Kentaro Shiraki; Effect of additives on liquid droplet of protein–polyelectrolyte complex for high-concentration formulations. J. Chem. Phys. 14 February 2019; 150 (6): 064903. https://doi.org/10.1063/1.5063378
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