کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10156864 | 1666435 | 2018 | 20 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Arginine suppresses opalescence and liquid-liquid phase separation in IgG solutions
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Antibody formulation often necessitates the protein concentration to be increased above 100â¯mg/ml, because of the large therapeutic doses of antibodies required and the volume limitations of subcutaneous injections. However, high concentrations of antibody lead to opalescent states in solution, resulting in safety and application problems. In this study, we investigated the effect of additives on opalescence in IgG solutions. Arginine (Arg) was observed to most effectively suppress opalescence in IgG solutions among the additives tested, which included guanidine hydrochloride, NaCl, and other amino acids. Moreover, Arg also suppressed liquid-liquid phase separation (LLPS) of highly concentrated IgG solutions during incubation at low temperature. Comparative analysis showed that the effects of Arg on opalescence and LLPS in IgG solutions result from its unique structure, which comprises an amino acid main chain, a guanidinium group, and a counter ion. These results indicate that Arg has high potency as an excipient in antibody drug formulations for the suppression of opalescence and LLPS as well as protein aggregation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 118, Part B, 15 October 2018, Pages 1708-1712
Journal: International Journal of Biological Macromolecules - Volume 118, Part B, 15 October 2018, Pages 1708-1712
نویسندگان
Shogo Oki, Suguru Nishinami, Kentaro Shiraki,