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Published Online: 12 February 2019
Accepted: January 2019

Effect of additives on liquid droplet of protein–polyelectrolyte complex for high-concentration formulations

J. Chem. Phys. 150, 064903 (2019); https://doi.org/10.1063/1.5063378
Masahiro Mimura1, Keisuke Tsumura1, Ayumi Matsuda1, Naoki Akatsuka2, and Kentaro Shiraki1,a)
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ABSTRACT
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.

ACKNOWLEDGMENTS

This work was partly supported by JSPS KAKENHI (Grant Nos. 18H02383 and 18H01719).

REFERENCES
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  1. 1. A. B. Kayitmazer, Adv. Colloid Interface Sci. 239, 169 (2017). https://doi.org/10.1016/j.cis.2016.07.006, Google ScholarCrossref
  2. 2. H. Morawetz and W. L. Hughes, Jr, J. Phys. Chem. 56, 69 (1952). https://doi.org/10.1021/j150493a014, Google ScholarCrossref
  3. 3. T. K. Kwan and J. -C. Kim, Biomacromolecules 12, 466 (2011). https://doi.org/10.1021/bm101249e, Google ScholarCrossref
  4. 4. S. Lankalapalli and V. R. M. Kolapalli, Indian J. Pharm. Sci. 71, 481 (2009). https://doi.org/10.4103/0250-474x.58165, Google ScholarCrossref
  5. 5. R. S. Stewart, C. S. Wang, and H. Shao, Adv. Colloid Interface Sci. 167, 85 (2011). https://doi.org/10.1016/j.cis.2010.10.009, Google ScholarCrossref
  6. 6. K. Shiraki, T. Kurinomaru, and S. Tomita, Curr. Med. Chem. 23, 276 (2016). https://doi.org/10.2174/0929867323666151127201126, Google ScholarCrossref
  7. 7. E. N. Savariar, S. Ghosh, D. C. Gonzalez, and S. Thayumanavan, J. Am. Chem. Soc. 130, 5416 (2008). https://doi.org/10.1021/ja800164z, Google ScholarCrossref
  8. 8. S. Tomita, O. Niwa, and R. Kurita, Anal. Chem. 88, 9079 (2016). https://doi.org/10.1021/acs.analchem.6b02010, Google ScholarCrossref
  9. 9. Y. Xu, M. Mazzawi, K. Chen, L. Sun, and P. L. Dubin, Biomacromolecules 12, 1512 (2011). https://doi.org/10.1021/bm101465y, Google ScholarCrossref
  10. 10. K. Iwashita, M. Mimura, and K. Shiraki, Curr. Pharm. Biotechnol. 19, 946–955 (2018). https://doi.org/10.2174/1389201020666181204113054, Google ScholarCrossref
  11. 11. F. Comert and P. L. Dubin, Adv. Colloid Interface Sci. 239, 213 (2017). https://doi.org/10.1016/j.cis.2016.08.005, Google ScholarCrossref
  12. 12. S. F. Banani, H. O. Lee, A. A. Hyman, and M. K. Rosen, Nat. Rev. Mol. Cell Biol. 18, 285 (2017). https://doi.org/10.1038/nrm.2017.7, Google ScholarCrossref
  13. 13. V. N. Uversky, Curr. Opin. Struct. Biol. 44, 18 (2016). https://doi.org/10.1016/j.sbi.2016.10.015, Google ScholarCrossref
  14. 14. A. A. Hyman, C. A. Weber, and F. Jülicher, Annu. Rev. Cell Dev. Biol. 30, 39 (2014). https://doi.org/10.1146/annurev-cellbio-100913-013325, Google ScholarCrossref
  15. 15. F. Comert, A. Y. Xu, S. P. Madro, V. Liadinskaia, and P. L. Dubin, J. Chem. Phys. 149, 163321 (2018). https://doi.org/10.1063/1.5029296, Google ScholarScitation, ISI
  16. 16. C. L. Cooper, P. L. Dubin, A. B. Kayitmazer, and S. Turksen, Curr. Opin. Colloid Interface Sci. 10, 52 (2005). https://doi.org/10.1016/j.cocis.2005.05.007, Google ScholarCrossref
  17. 17. T. Kurinomaru and K. Shiraki, Int. J. Biol. Macromol. 100, 11 (2017). https://doi.org/10.1016/j.ijbiomac.2016.06.016, Google ScholarCrossref
  18. 18. T. Kurinomaru, T. Maruyama, S. Izaki, K. Handa, T. Kimoto, and K. Shiraki, J. Pharm. Sci. 103, 2248 (2014). https://doi.org/10.1002/jps.24025, Google ScholarCrossref
  19. 19. A. Filenko, M. Demchenko, Z. Mustafaeva, Y. Osada, and M. Mustafaev, Biomacromolecules 2, 270 (2001). https://doi.org/10.1021/bm000111q, Google ScholarCrossref
  20. 20. S. Oki, K. Iwashita, M. Kimura, H. Kano, and K. Shiraki, Int. J. Biol. Macromol. 107, 1428 (2018). https://doi.org/10.1016/j.ijbiomac.2017.10.004, Google ScholarCrossref
  21. 21. A. Matsuda, M. Mimura, T. Maruyama, T. Kurinomaru, M. Shiuhei, and K. Shiraki, J. Pharm. Sci. 107, 2713 (2018). https://doi.org/10.1016/j.xphs.2018.06.021, Google ScholarCrossref
  22. 22. T. Arakawa and S. N. Timasheff, Biochemistry 21, 6536 (1982). https://doi.org/10.1021/bi00268a033, Google ScholarCrossref
  23. 23. T. Arakawa and S. N. Timasheff, Biochemistry 24, 6756 (1985). https://doi.org/10.1021/bi00345a005, Google ScholarCrossref
  24. 24. S. Moelbert, B. Normand, and P. D. L. Rios, Biophys. Chem. 112, 45 (2014). https://doi.org/10.1016/j.bpc.2004.06.012, Google ScholarCrossref
  25. 25. K. Shiraki, M. Kudou, S. Fujiwara, T. Imanaka, and M. Takagi, J. Biochem. 132, 591 (2002). https://doi.org/10.1093/oxfordjournals.jbchem.a003261, Google ScholarCrossref
  26. 26. S. Yoshizawa, T. Arakawa, and K. Shiraki, Int. J. Biol. Macromol. 104, 650 (2017). https://doi.org/10.1016/j.ijbiomac.2017.06.085, Google ScholarCrossref
  27. 27. T. Miyatake, S. Yoshizawa, T. Arakawa, and K. Shiraki, Int. J. Biol. Macromol. 87, 563 (2016). https://doi.org/10.1016/j.ijbiomac.2016.03.015, Google ScholarCrossref
  28. 28. T. Arakawa and S. N. Timasheff, Biophys. J. 47, 411 (1985). https://doi.org/10.1016/s0006-3495(85)83932-1, Google ScholarCrossref
  29. 29. H.-I. Chen and H.-Y. Chang, Colloids Surf. A Physicochem. Eng. Asp. 242, 61 (2004). https://doi.org/10.1016/j.colsurfa.2004.04.056, Google ScholarCrossref
  30. 30. S. Yoshizawa, T. Arakawa, and K. Shiraki, Int. J. Biol. Macromol. 68, 169 (2014). https://doi.org/10.1016/j.ijbiomac.2014.04.041, Google ScholarCrossref
  31. 31. N. Hirota, K. Mizuno, and Y. Goto, J. Mol. Biol. 275, 365 (1998). https://doi.org/10.1006/jmbi.1997.1468, Google ScholarCrossref
  32. 32. T. J. Kamerzell, R. Esfandiary, S. B. Joshi, C. R. Middaugh, and D. B. Volkin, Adv. Drug Deliv. Rev. 63, 1118 (2011). https://doi.org/10.1016/j.addr.2011.07.006, Google ScholarCrossref
  33. 33. D. H. Atha and K. C. Ingham, J. Biol. Chem. 256, 12108 (1981), available at http://www.jbc.org/content/256/23/12108.abstract. Google Scholar
  34. 34. M. J. Akers, J. Pharm. Sci. 91, 2283 (2002). https://doi.org/10.1002/jps.10154, Google ScholarCrossref
  35. 35. W. Wang, S. Singh, D. L. Zeng, K. King, and S. Nema, J. Pharm. Sci. 96, 1 (2007). https://doi.org/10.1002/jps.20727, Google ScholarCrossref
  36. 36. L. L. Chang, D. Shepherd, J. Sun, X. C. Tang, and M. J. Pikal, J. Pharm. Sci. 94, 1445 (2005). https://doi.org/10.1002/jps.20363, Google ScholarCrossref
  37. 37. W. Wang, Int. J. Pharm. 289, 1 (2005). https://doi.org/10.1016/j.ijpharm.2004.11.014, Google ScholarCrossref
  38. 38. C. L. Cooper, A. Goulding, A. B. Kayitmazer, S. Ulrich, S. Stoll, S. Turksen, S. Yusa, A. Kumar, and P. L. Dubin, Biomacromolecules 7, 1025 (2006). https://doi.org/10.1021/bm050592j, Google ScholarCrossref
  39. 39. E. Seyrek, P. L. Dubin, C. Tribet, and E. A. Gamble, Biomacromolecules 4, 273 (2003). https://doi.org/10.1021/bm025664a, Google ScholarCrossref
  40. 40. S. Uchiyama, Biochim. Biophys. Acta 1844, 2041 (2014). https://doi.org/10.1016/j.bbapap.2014.07.016, Google ScholarCrossref
  41. 41. P. Zhang, K. Shen, N. M. Alsaifi, and Z.-G. Wang, Macromolecules 51, 5586 (2018). https://doi.org/10.1021/acs.macromol.8b00726, Google ScholarCrossref
  42. 42. M. Krishnan, J. Chem. Phys. 146, 205101 (2017). https://doi.org/10.1063/1.4983485, Google ScholarScitation, ISI
  43. 43. M. L. Tiffany and S. Krimm, Biopolymers 6, 1379 (1968). https://doi.org/10.1002/bip.1968.360060911, Google ScholarCrossref
  44. 44. Y.-H. Chen, J. T. Yang, and H. M. Martinez, Biochem 11, 4120 (1972). https://doi.org/10.1021/bi00772a015, Google ScholarCrossref
  45. 45. H. Yoshikawa, A. Hirano, T. Arakawa, and K. Shiraki, Int. J. Biol. Macromol. 50, 1286 (2012). https://doi.org/10.1016/j.ijbiomac.2012.03.014, Google ScholarCrossref
  46. 46. S. L. Perry, Y. Li, D. Priftis, L. Leon, and M. Tirrell, Polymers 6, 1756 (2014). https://doi.org/10.3390/polym6061756, Google ScholarCrossref
  47. 47. D. Bertolini, M. Cassettari, and G. Salvetti, J. Chem. Phys. 78, 365 (1983). https://doi.org/10.1063/1.444510, Google ScholarScitation, ISI
  48. 48. P. L. Dubin, J. Gao, and K. Mattison, Sep. Purif. Methods 23, 1 (1994). https://doi.org/10.1080/03602549408001288, Google ScholarCrossref
  49. 49. B. I. M. Wickya, S. L. Shammasa, and J. Clarke, Proc. Natl. Acad. Sci. U. S. A. 114, 9882 (2017). https://doi.org/10.1073/pnas.1705105114, Google ScholarCrossref
  50. 50. P. H. Yancey, M. E. Clark, S. C. Hand, R. D. Bowlus, and G. N. Somero, Science 217, 1214 (1982). https://doi.org/10.1126/science.7112124, Google ScholarCrossref
  51. 51. G. V. Barnett, V. I. Razinko, B. A. Kerwi, S. Blak, W. Q., R. A. Curti, and C. J. Roberts, J. Phys. Chem. B 120, 3318 (2016). https://doi.org/10.1021/acs.jpcb.6b00621, Google ScholarCrossref
  52. 52. J. A. Riback, C. D. Katanski, J. L. Kear-Scott, E. V. Pilipenko, A. E. Rojek, T. R. Sosnick, and D. A. Drummond, Cell 168, 1028 (2017). https://doi.org/10.1016/j.cell.2017.02.027, Google ScholarCrossref
  53. 53. S. Boeynaems, S. Alberti, N. L. Fawzi, T. Mittag, M. Polymenidou, F. Rousseau, J. Schymkowitz, J. Shorter, B. Wolozin, L. V. D. Bosch, and P. Tompa, Trends Cell Biol. 28, 420 (2018). https://doi.org/10.1016/j.tcb.2018.02.004, Google ScholarCrossref
  54. 54. M. Chao and N. S. Zacharia, J. Chem. Phys. 149, 163326 (2018). https://doi.org/10.1063/1.5040346, Google ScholarScitation
  55. 55. S. Izaki, T. Kurinomaru, K. Handa, T. Kimoto, and K. Shiraki, J. Pharm. Sci. 104, 2457 (2015). https://doi.org/10.1002/jps.24515, Google ScholarCrossref
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