Effect of Sugar Molecules on the Viscosity of High Concentration Monoclonal Antibody Solutions
Effect of Sugar Molecules on the Viscosity of High Concentration Monoclonal Antibody Solutions
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DOI：
10.1007/s11095-011-0388-7
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发表时间：
2011-07-01
影响因子：
3.7
通讯作者：
Kerwin, Bruce A.
中科院分区：
文献类型：
--
作者：
He, Feng;Woods, Christopher E.;Kerwin, Bruce A.
评价糖分子在高蛋白质浓度下对溶液粘度的影响。采用高通量动态光散射法测定单克隆抗体溶液的粘度。考察了蛋白质浓度、糖分子类型（海藻糖、蔗糖、山梨醇、葡萄糖、果糖、木糖和半乳糖）、温度和离子强度的影响。差示扫描荧光法用于揭示相同的糖对蛋白质稳定性的影响，并提供糖增加粘度的机制的见解。所研究的所有七种糖分子的加入导致高浓度单克隆抗体溶液粘度的显著增加。在检测的两种单抗中观察到糖的类似作用；可以通过提高离子强度或温度来降低粘度。蛋白质浓度越高，糖的作用越明显。与单糖相比，双糖在高蛋白质浓度下对溶液粘度的影响更大。这种效应可以用溶液中糖和蛋白质分子相互作用的普遍机制来解释。
To assess the effect of sugar molecules on solution viscosity at high protein concentrations.A high throughput dynamic light scattering method was used to measure the viscosity of monoclonal antibody solutions. The effects of protein concentration, type of sugar molecule (trehalose, sucrose, sorbitol, glucose, fructose, xylose and galactose), temperature and ionic strength were evaluated. Differential scanning fluorimetry was used to reveal the effect of the same sugars on protein stability and to provide insight into the mechanism by which sugars increase viscosity.The addition of all seven types of sugar molecules studied result in a significant increase in viscosity of high concentration monoclonal antibody solutions. Similar effects of sugars were observed in the two mAbs examined; viscosity could be reduced by increasing the ionic strength or temperature. The effect by sugars was enhanced at higher protein concentrations.Disaccharides have a greater effect on the solution viscosity at high protein concentrations compared to monosaccharides. The effect may be explained by commonly accepted mechanisms of interactions between sugar and protein molecules in solution.